[Current events in vaccination].

PubMed

Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J L; Strady, C

2011-05-01

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

Vector-based genetically modified vaccines: Exploiting Jenner's legacy.

PubMed

Ramezanpour, Bahar; Haan, Ingrid; Osterhaus, Ab; Claassen, Eric

2016-12-07

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors

[Development of current smallpox vaccines].

PubMed

Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

2011-01-01

The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

Biomaterials at the interface of nano- and micro-scale vector-cellular interactions in genetic vaccine design.

PubMed

Jones, Charles H; Hakansson, Anders P; Pfeifer, Blaine A

2014-01-01

The development of safe and effective vaccines for the prevention of elusive infectious diseases remains a public health priority. Immunization, characterized by adaptive immune responses to specific antigens, can be raised by an array of delivery vectors. However, current commercial vaccination strategies are predicated on the retooling of archaic technology. This review will discuss current and emerging strategies designed to elicit immune responses in the context of genetic vaccination. Selected strategies at the biomaterial-biological interface will be emphasized to illustrate the potential of coupling both fields towards a common goal.

Genetic characterization of L-Zagreb mumps vaccine strain.

PubMed

Ivancic, Jelena; Gulija, Tanja Kosutic; Forcic, Dubravko; Baricevic, Marijana; Jug, Renata; Mesko-Prejac, Majda; Mazuran, Renata

2005-04-01

Eleven mumps vaccine strains, all containing live attenuated virus, have been used throughout the world. Although L-Zagreb mumps vaccine has been licensed since 1972, only its partial nucleotide sequence was previously determined (accession numbers , and ). Therefore, we sequenced the entire genome of L-Zagreb vaccine strain (Institute of Immunology Inc., Zagreb, Croatia). In order to investigate the genetic stability of the vaccine, sequences of both L-Zagreb master seed and currently produced vaccine batch were determined and no difference between them was observed. A phylogenetic analysis based on SH gene sequence has shown that L-Zagreb strain does not belong to any of established mumps genotypes and that it is most similar to old, laboratory preserved European strains (1950s-1970s). L-Zagreb nucleotide and deduced protein sequences were compared with other mumps virus sequences obtained from the GenBank. Emphasis was put on functionally important protein regions and known antigenic epitopes. The extensive comparisons of nucleotide and deduced protein sequences between L-Zagreb vaccine strain and other previously determined mumps virus sequences have shown that while the functional regions of HN, V, and L proteins are well conserved among various mumps strains, there can be a substantial amino acid difference in antigenic epitopes of all proteins and in functional regions of F protein. No molecular pattern was identified that can be used as a distinction marker between virulent and attenuated strains.

Current Status of Veterinary Vaccines

PubMed Central

Meeusen, Els N. T.; Walker, John; Peters, Andrew; Pastoret, Paul-Pierre; Jungersen, Gregers

2007-01-01

The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases. PMID:17630337

Biological safety concepts of genetically modified live bacterial vaccines.

PubMed

Frey, Joachim

2007-07-26

Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment

Limited genetic and antigenic diversity within parasite isolates used in a live vaccine against Theileria parva.

PubMed

Hemmink, Johanneke D; Weir, William; MacHugh, Niall D; Graham, Simon P; Patel, Ekta; Paxton, Edith; Shiels, Brian; Toye, Philip G; Morrison, W Ivan; Pelle, Roger

2016-07-01

An infection and treatment protocol is used to vaccinate cattle against Theileria parva infection. Due to incomplete cross-protection between different parasite isolates, a mixture of three isolates, termed the Muguga cocktail, is used for vaccination. While vaccination of cattle in some regions provides high levels of protection, some animals are not protected against challenge with buffalo-derived T. parva. Knowledge of the genetic composition of the Muguga cocktail vaccine is required to understand how vaccination is able to protect against field challenge and to identify the potential limitations of the vaccine. The aim of the current study was to determine the extent of genetic and antigenic diversity within the parasite isolates that constitute the Muguga cocktail. High throughput multi-locus sequencing of antigen-encoding loci was performed in parallel with typing using a panel of micro- and mini-satellite loci. The former focused on genes encoding CD8(+) T cell antigens, believed to be relevant to protective immunity. The results demonstrate that each of the three component stocks of the cocktail contains limited parasite genotypic diversity, with single alleles detected at many gene/satellite loci and, moreover, that two of the components show a very high level of similarity. Thus, the vaccine incorporates very little of the genetic and antigenic diversity observed in field populations of T. parva. The presence of alleles at low frequency (<10%) within vaccine component populations also points to the possibility of variability in the content of vaccine doses and the potential for loss of allelic diversity during tick passage. The results demonstrate that there is scope to modify the content of the vaccine in order to enhance its diversity and thus its potential for providing broad protection. The ability to accurately quantify genetic diversity in vaccine component stocks will facilitate improved quality control procedures designed to ensure the long

Autism and vaccination-the current evidence.

PubMed

Miller, Lisa; Reynolds, Joni

2009-07-01

The purpose of this article is to review relevant background literature regarding the evidence linking thimerosal-containing vaccine and the measles, mumps, and rubella vaccine to autism. Rigorous scientific studies have not identified links between autism and either thimerosal-containing vaccine or the measles, mumps, and rubella vaccine. Nurses are often in the position of providing advice regarding vaccines in their formal practice areas as well as in their daily lives. Families need current and credible evidence to make decisions for their children. Excellent vaccine information resources are available online.

Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014–2015

PubMed Central

Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.

2018-01-01

Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176

From The Cover: Poly- amino ester-containing microparticles enhance the activity of nonviral genetic vaccines

NASA Astrophysics Data System (ADS)

Little, Steven R.; Lynn, David M.; Ge, Qing; Anderson, Daniel G.; Puram, Sidharth V.; Chen, Jianzhu; Eisen, Herman N.; Langer, Robert

2004-06-01

Current nonviral genetic vaccine systems are less effective than viral vaccines, particularly in cancer systems where epitopes can be weakly immunogenic and antigen-presenting cell processing and presentation to T cells is down-regulated. A promising nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect plasmid payloads and target them to phagocytic antigen-presenting cells. However, conventional microparticle formulations composed of poly lactic-co-glycolic acid take too long to release encapsulated payload and fail to induce high levels of target gene expression. Here, we describe a microparticle-based DNA delivery system composed of a degradable, pH-sensitive poly- amino ester and poly lactic-co-glycolic acid. These formulations generate an increase of 3-5 orders of magnitude in transfection efficiency and are potent activators of dendritic cells in vitro. When used as vaccines in vivo, these microparticle formulations, unlike conventional formulations, induce antigen-specific rejection of transplanted syngenic tumor cells.

Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

PubMed Central

2012-01-01

Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus

Update on the current status of cytomegalovirus vaccines.

PubMed

Sung, Heungsup; Schleiss, Mark R

2010-11-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Update on the current status of cytomegalovirus vaccines

PubMed Central

Sung, Heungsup; Schleiss, Mark R

2013-01-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design. PMID:21087108

Use of a current varicella vaccine as a live polyvalent vaccine vector.

PubMed

Murakami, Kouki; Mori, Yasuko

2016-01-04

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

The delicate balance in genetically engineering live vaccines

PubMed Central

Galen, James E.; Curtiss, Roy

2014-01-01

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health. PMID:24370705

Reverse Genetics for Newcastle Disease Virus as a Vaccine Vector.

PubMed

Kim, Shin-Hee; Samal, Siba K

2018-02-22

Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e.g., LaSota and B1) have been commonly used as vaccine vectors. In this protocol, we have described reverse genetics of NDV to be used as a vaccine vector by exemplifying the recovery of NDV vectored avian influenza virus vaccine. Specifically, cloning and recovery of NDV expressing the hemagglutinin protein of highly pathogenic influenza virus were explained. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Current safety issues with quadrivalent meningococcal conjugate vaccines.

PubMed

Myers, Tanya R; McNeil, Michael M

2018-05-04

Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra® (Sanofi Pasteur) and Menveo® (GlaxoSmithKline), and usage in the adolescent population has steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barré syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell's palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

Development of improved vaccines against whooping cough: current status.

PubMed

Marzouqi, Ibrahim; Richmond, Peter; Fry, Scott; Wetherall, John; Mukkur, Trilochan

2010-07-01

Prior to the introduction of killed whole cell pertussis vaccine [wP] in the 1940s, whooping cough was a major cause of infant death worldwide. Widespread vaccination of children with this vaccine caused a significant reduction in mortality. However in the 1990s and now more recently, there has been a resurgence of pertussis in several countries even in populations previously vaccinated with an acellular pertussis vaccine [aP]. In this review, we describe the epidemiology of whooping cough, the vast array of virulence factors produced by this pathogen potentially contributing to the resurgence of pertussis even in previously vaccinated populations of infants and children, history of whooping cough prophylaxis, possible mechanisms of immunity, lack of availability of a suitable non-toxic adjuvant capable of inducing both arms of the immune response, and the current status of development of improved vaccines with potential to induce longer-lasting protection, than is currently possible with the wP or aP vaccines, against whooping cough.

Genetically defined race, but not sex, is associated with higher humoral and cellular immune responses to measles vaccination

PubMed Central

Voigt, Emily A.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Kennedy, Richard B.; Larrabee, Beth R.; Schaid, Daniel J.; Poland, Gregory A.

2017-01-01

In addition to host genetic and environmental factors, variations in immune responses to vaccination are influenced by demographic variables, such as race and sex. The influence of genetic race and sex on measles vaccine responses is not well understood, yet important for the development of much-needed improved measles vaccines with lower failure rates. We assessed associations between genetically defined race and sex with measles humoral and cellular immunity after measles vaccination in three independent and geographically distinct cohorts totaling 2,872 healthy racially diverse children, older adolescents, and young adults. We found no associations between biological sex and either humoral or cellular immunity to measles vaccine, and no correlation between humoral and cellular immunity in these study subjects. Genetically defined race was, however, significantly associated with both measles vaccine-induced humoral and cellular immune responses, with subjects genetically classified as having African-American ancestry demonstrating significantly higher antibody and cell-mediated immune responses relative to subjects of Caucasian ancestry. This information may be useful in designing novel measles vaccines that are optimally effective across human genetic backgrounds. PMID:27591105

Genetic stability of a dengue vaccine based on chimeric yellow fever/dengue viruses.

PubMed

Mantel, N; Girerd, Y; Geny, C; Bernard, I; Pontvianne, J; Lang, J; Barban, V

2011-09-02

A tetravalent dengue vaccine based on four live, attenuated, chimeric viruses (CYD1-4), constructed by replacing the genes coding for premembrane (prM) and envelope (E) proteins of the yellow fever (YF)-17D vaccine strain with those of the four serotypes of dengue virus, is in clinical phase III evaluation. We assessed the vaccine's genetic stability by fully sequencing each vaccine virus throughout the development and manufacturing process. The four viruses displayed complete genetic stability, with no change from premaster seed lots to bulk lots. When pursuing the virus growth beyond bulk lots, a few genetic variations were observed. Usually both the initial nucleotide and the new one persisted, and mutations appeared after a relatively high number of virus duplication cycles (65-200, depending on position). Variations were concentrated in the prM-E and non-structural (NS)4B regions. PrM-E variations had no impact on lysis-plaque size or neurovirulence in mice. None of the variations located in the YF-17D-derived genes corresponded with reversion to the wild-type Yellow Fever sequence. Variations in NS4B likely reflect virus adaptation to Vero cells growth. A low to undetectable viremia has been reported previously [1-3] in vaccinated non-human and human primates. Combined with the data reported here about the genetic stability of the vaccine strains, the probability of in vivo emergence of mutant viruses appears very low. Copyright © 2011 Elsevier Ltd. All rights reserved.

Current biodefense vaccine programs and challenges.

PubMed

Wolfe, Daniel N; Florence, William; Bryant, Paula

2013-07-01

The Defense Threat Reduction Agency's Joint Science and Technology Office manages the Chemical and Biological Defense Program's Science and Technology portfolio. The Joint Science and Technology Office's mission is to invest in transformational ideas, innovative people and actionable technology development for Chemical and Biological Defense solutions, with the primary goal to deliver Science and Technology products and capabilities to the warfighter and civilian population that outpace the threat. This commentary focuses on one thrust area within this mission: the Vaccine program of the Joint Science and Technology Office's Translational Medical Division. Here, we will describe candidate vaccines currently in the S&T pipeline, enabling technologies that should facilitate advanced development of these candidates into FDA licensed vaccines, and how the ever-changing biological threat landscape impacts the future of biodefense vaccines.

Cancer Vaccines: Moving Beyond Current Paradigms

PubMed Central

Schlom, Jeffrey; Arlen, Philip M.; Gulley, James L.

2008-01-01

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. While no therapeutic cancer vaccine has to date been approved by the FDA, several new paradigms are emerging from recent clinical findings in both the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and endpoint analyses. This paper will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classical “tumor response” (RECIST) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies, and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies. PMID:17606707

Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status.

PubMed

Moore, Michael C; Davis, Rolan D; Kang, Qing; Vahl, Christopher I; Wallace, Ryan M; Hanlon, Cathleen A; Mosier, Derek A

2015-01-15

To compare anamnestic antibody responses of dogs and cats with current versus out-of-date vaccination status. Cross-sectional study. 74 dogs and 33 cats. Serum samples were obtained from dogs and cats that had been exposed to rabies and brought to a veterinarian for proactive serologic monitoring or that had been brought to a veterinarian for booster rabies vaccination. Blood samples were collected on the day of initial evaluation (day 0) and then again 5 to 15 days later. On day 0, a rabies vaccine was administered according to label recommendations. Paired serum samples were analyzed for antirabies antibodies by means of a rapid fluorescent focus inhibition test. All animals had an antirabies antibody titer ≥ 0.5 IU/mL 5 to 15 days after booster vaccination. Dogs with an out-of-date vaccination status had a higher median increase in titer, higher median fold increase in titer, and higher median titer following booster vaccination, compared with dogs with current vaccination status. Most (26/33) cats, regardless of rabies vaccination status, had a titer ≥ 12 IU/mL 5 to 15 days after booster vaccination. Results indicated that dogs with out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination, compared with dogs with current vaccination status. Findings supported immediate booster vaccination followed by observation for 45 days of dogs and cats with an out-of-date vaccination status that are exposed to rabies, as is the current practice for dogs and cats with current vaccination status.

Genetic Polymorphisms Associated with Rubella Virus-Specific Cellular Immunity Following MMR Vaccination

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Lambert, Nathaniel D.; Pankratz, V. Shane; Poland, Gregory A.

2014-01-01

Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single dose seroconversion rates ~95%. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects ages 11–22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (ages 18–40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination. PMID:25098560

Genetic polymorphisms associated with rubella virus-specific cellular immunity following MMR vaccination.

PubMed

Kennedy, Richard B; Ovsyannikova, Inna G; Haralambieva, Iana H; Lambert, Nathaniel D; Pankratz, V Shane; Poland, Gregory A

2014-11-01

Rubella virus causes a relatively benign disease in most cases, although infection during pregnancy can result in serious birth defects. An effective vaccine has been available since the early 1970s and outbreaks typically do not occur among highly vaccinated (≥2 doses) populations. Nevertheless, considerable inter-individual variation in immune response to rubella immunization does exist, with single-dose seroconversion rates ~95 %. Understanding the mechanisms behind this variability may provide important insights into rubella immunity. In the current study, we examined associations between single nucleotide polymorphisms (SNPs) in selected cytokine, cytokine receptor, and innate/antiviral genes and immune responses following rubella vaccination in order to understand genetic influences on vaccine response. Our approach consisted of a discovery cohort of 887 subjects aged 11-22 at the time of enrollment and a replication cohort of 542 older adolescents and young adults (age 18-40). Our data indicate that SNPs near the butyrophilin genes (BTN3A3/BTN2A1) and cytokine receptors (IL10RB/IFNAR1) are associated with variations in IFNγ secretion and that multiple SNPs in the PVR gene, as well as SNPs located in the ADAR gene, exhibit significant associations with rubella virus-specific IL-6 secretion. This information may be useful, not only in furthering our understanding immune responses to rubella vaccine, but also in identifying key pathways for targeted adjuvant use to boost immunity in those with weak or absent immunity following vaccination.

Meningococcal vaccines: Current state and future outlook.

PubMed

Leca, M; Bornet, C; Montana, M; Curti, C; Vanelle, P

2015-06-01

Neisseria meningitidis infections are a major public health problem worldwide. Although conventional approaches have not led to development of a serogroup B meningococcal vaccine, a new technique based on genome sequencing has created new perspectives. Recently, a universal serogroup B meningococcal vaccine, Bexsero(®), was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety. Availability of this vaccine could contribute positively to human health, by significantly reducing the incidence of meningococcal infections. However, unfavorable cost-effectiveness analysis means that routine vaccination is not currently recommended. Another serogroup meningococcal vaccine, Trumemba(®), was also recently licensed in United States. Like any drug, Bexsero(®) and Trumemba(®) will require close observation to assess their impact on meningococcal epidemiology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Genetically detoxified pertussis toxin (PT-9K/129G): implications for immunization and vaccines.

PubMed

Seubert, Anja; D'Oro, Ugo; Scarselli, Maria; Pizza, Mariagrazia

2014-10-01

Pertussis toxin (PT) is one of the major virulence factors of Bordetella pertussis and the primary component of all pertussis vaccines available to date. Because of its various noxious effects the toxin needs to be detoxified. In all currently available vaccines, detoxification is achieved by treatment with high quantity of chemical agents such as formaldehyde, glutaraldehyde or hydrogen peroxide. Although effective in detoxification, this chemical treatment alters dramatically the immunological properties of the toxin. In contrast, PT genetically detoxified through the substitution of two residues necessary for its enzymatic activity maintains all functional and immunological properties. This review describes in detail the characteristics of this PT-9K/129G mutant and shows that it is non-toxic and a superior immunogen compared with chemically detoxified PT. Importantly, data from an efficacy trial show that the PT-9K/129G-based vaccine induces earlier and longer-lasting protection, further supporting the hypothesis that PT-9K/129G represents an ideal candidate for future pertussis vaccine formulations.

Vaccines Against Malaria

PubMed Central

Ouattara, Amed; Laurens, Matthew B.

2015-01-01

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

[Rabies vaccines: Current status and prospects for development].

PubMed

Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

2015-01-01

Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

Vaccination for Disease

NASA Astrophysics Data System (ADS)

Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

1991-01-01

Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

How can plant genetic engineering contribute to cost-effective fish vaccine development for promoting sustainable aquaculture?

PubMed

Clarke, Jihong Liu; Waheed, Mohammad Tahir; Lössl, Andreas G; Martinussen, Inger; Daniell, Henry

2013-09-01

Aquaculture, the fastest growing food-producing sector, now accounts for nearly 50 % of the world's food fish (FAO in The state of world fisheries and aquaculture. FAO, Rome, 2010). The global aquaculture production of food fish reached 62.7 million tonnes in 2011 and is continuously increasing with an estimated production of food fish of 66.5 million tonnes in 2012 (a 9.4 % increase in 1 year, FAO, www.fao.org/fishery/topic/16140 ). Aquaculture is not only important for sustainable protein-based food fish production but also for the aquaculture industry and economy worldwide. Disease prevention is the key issue to maintain a sustainable development of aquaculture. Widespread use of antibiotics in aquaculture has led to the development of antibiotic-resistant bacteria and the accumulation of antibiotics in the environment, resulting in water and soil pollution. Thus, vaccination is the most effective and environmentally-friendly approach to combat diseases in aquaculture to manage fish health. Furthermore, when compared to >760 vaccines against human diseases, there are only about 30 fish vaccines commercially available, suggesting the urgent need for development and cost-effective production of fish vaccines for managing fish health, especially in the fast growing fish farming in Asia where profit is minimal and therefore given high priority. Plant genetic engineering has made significant contributions to production of biotech crops for food, feed, valuable recombinant proteins etc. in the past three decades. The use of plants for vaccine production offers several advantages such as low cost, safety and easy scaling up. To date a large number of plant-derived vaccines, antibodies and therapeutic proteins have been produced for human health, of which a few have been made commercially available. However, the development of animal vaccines in plants, especially fish vaccines by genetic engineering, has not yet been addressed. Therefore, there is a need to exploit

Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction.

PubMed

Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

2015-08-07

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork

HIV vaccines: current challenges and future directions.

PubMed

Avrett, Sam; Collins, Chris

2002-07-01

Volume seven of the Review will mark the tenth anniversary of the Canadian HIV/AIDS Legal Network with a series of articles that describe past developments and future directions in several areas of policy and law related to HIV/AIDS. The following article is the first of these, discussing current challenges and future directions in the development of and access to HIV vaccines. It argues that governments are under public health, ethical, and legal obligations to develop and provide access to HIV vaccines. It further explains what is required for governments to fulfill their obligations: additional commitment and resources for HIV vaccine development in the context of increased global research and development regarding diseases of the poor; increased support and advocacy for partnerships to develop HIV vaccines; enhanced regulatory capacity in every country to review, approve, and monitor HIV vaccines; and assurance of global supply of, procurement of, delivery of, and access to vaccines in the context of efforts to increase global access to public health measures and technologies.

Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

ERIC Educational Resources Information Center

Farizo, Karen M.; And Others

1990-01-01

Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

Current status of new tuberculosis vaccine in children

PubMed Central

Pang, Yu; Zhao, Aihua; Cohen, Chad; Kang, Wanli; Lu, Jie; Wang, Guozhi; Zhao, Yanlin; Zheng, Suhua

2016-01-01

ABSTRACT Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children. PMID:27002369

Evolution of the Sabin vaccine into pathogenic derivatives without appreciable changes in antigenic properties: need for improvement of current poliovirus surveillance.

PubMed

Yakovenko, Maria L; Korotkova, Ekaterina A; Ivanova, Olga E; Eremeeva, Tatyana P; Samoilovich, Elena; Uhova, Iryna; Gavrilin, Gene V; Agol, Vadim I

2009-04-01

The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with "Sabin-like" properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV.

HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine

PubMed Central

Zhu, Xiao-Peng; Muhammad, Zaka S.; Wang, Jian-Guang; Lin, Wu; Guo, Shi-Kun; Zhang, Wei

2014-01-01

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines. PMID:24469503

Engineering of Genetically Arrested Parasites (GAPs) For a Precision Malaria Vaccine.

PubMed

Kreutzfeld, Oriana; Müller, Katja; Matuschewski, Kai

2017-01-01

Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential. A better understanding of the immunological mechanisms of prime and boost by arrested sporozoites and experimental strategies to enhance vaccine efficacy by further engineering existing GAPs into a more immunogenic form hold promise for continuous improvements of GAP-based vaccines. A critical hurdle for vaccines that elicit long-lasting protection against malaria, such as GAPs, is safety and efficacy in vulnerable populations. Vaccine research should focus on solutions toward turning malaria into a vaccine-preventable disease, which would offer an exciting new path of malaria control.

Finding optimal vaccination strategies for pandemic influenza using genetic algorithms.

PubMed

Patel, Rajan; Longini, Ira M; Halloran, M Elizabeth

2005-05-21

In the event of pandemic influenza, only limited supplies of vaccine may be available. We use stochastic epidemic simulations, genetic algorithms (GA), and random mutation hill climbing (RMHC) to find optimal vaccine distributions to minimize the number of illnesses or deaths in the population, given limited quantities of vaccine. Due to the non-linearity, complexity and stochasticity of the epidemic process, it is not possible to solve for optimal vaccine distributions mathematically. However, we use GA and RMHC to find near optimal vaccine distributions. We model an influenza pandemic that has age-specific illness attack rates similar to the Asian pandemic in 1957-1958 caused by influenza A(H2N2), as well as a distribution similar to the Hong Kong pandemic in 1968-1969 caused by influenza A(H3N2). We find the optimal vaccine distributions given that the number of doses is limited over the range of 10-90% of the population. While GA and RMHC work well in finding optimal vaccine distributions, GA is significantly more efficient than RMHC. We show that the optimal vaccine distribution found by GA and RMHC is up to 84% more effective than random mass vaccination in the mid range of vaccine availability. GA is generalizable to the optimization of stochastic model parameters for other infectious diseases and population structures.

Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

PubMed Central

Sack, David A.

2015-01-01

Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID:26135975

Development of a Genetically Engineered Venezuelan Equine Encephalitis Virus Vaccine

DTIC Science & Technology

1988-12-20

immunization, the horses will be returned to the large animal biocontainment facility to be challenged with equine virulent VEE virus. The animals will be...AD £IT FiLE C p DEVELOPMENT OF A GENETICALLY ENGINEERED VENEZUELAN EQUINE ENCEPHALITIS VIRUS VACCINE ANNUAL REPORT to DENNIS W. TRENT 0DECEMBER 20...Engineered Venezuelan Equine Encephalitis Virus Vaccine 12. PERSONAL AUTHOR(S) Dennis W. Trent 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT

Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice.

PubMed

Rodrigues, Mauricio M; de Alencar, Bruna C; Claser, Carla; Tzelepis, Fanny; Silveira, Eduardo L; Haolla, Filipe A; Dominguez, Mariana R; Vasconcelos, José Ronnie

2009-07-01

Vaccines have had an unquestionable impact on public health during the last century. The most likely reason for the success of vaccines is the robust protective properties of specific antibodies. However, antibodies exert a strong selective pressure and many microorganisms, such as the obligatory intracellular parasite Trypanosoma cruzi, have been selected to survive in their presence. Although the host develops a strong immune response to T. cruzi, they do not clear the infection and instead progress to the chronic phase of the disease. Parasite persistence during the chronic phase of infection is now considered the main factor contributing to the chronic symptoms of the disease. Based on this finding, containment of parasite growth and survival may be one method to avoid the immunopathology of the chronic phase. In this context, vaccinologists have looked over the past 20 years for other immune effector mechanisms that could eliminate these antibody-resistant pathogens. We and others have tested the hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could indeed be used for the purpose of vaccination. This hypothesis was confirmed in different mouse models, indicating a possible path for vaccine development.

Dengue vaccines: recent developments, ongoing challenges and current candidates

PubMed Central

McArthur, Monica A.; Sztein, Marcelo B.; Edelman, Robert

2013-01-01

Summary Dengue is among the most prevalent and important arbovirus diseases of humans. In order to effectively control this rapidly spreading disease, control of the vector mosquito and a safe and efficacious vaccine are critical. Despite considerable efforts, the development of a successful vaccine has remained elusive. Multiple factors have complicated the creation of a successful vaccine, not the least of which are the complex, immune-mediated responses against four antigenically distinct serotypes necessitating a tetravalent vaccine providing long lasting protective immunity. Despite the multiple impediments, there are currently many promising vaccine candidates in pre-clinical and clinical development. Here we review the recent advances in dengue virus vaccine development and briefly discuss the challenges associated with the use of these vaccines as a public health tool. PMID:23984962

Lactococcus lactis-based vaccines: current status and future perspectives.

PubMed

Bahey-El-Din, Mohammed; Gahan, Cormac G M

2011-01-01

Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.

Live vaccines for human metapneumovirus designed by reverse genetics.

PubMed

Buchholz, Ursula J; Nagashima, Kunio; Murphy, Brian R; Collins, Peter L

2006-10-01

Human metapneumovirus (HMPV) was first described in 2001 and has quickly become recognized as an important cause of respiratory tract disease worldwide, especially in the pediatric population. A vaccine against HMPV is required to prevent severe disease associated with infection in infancy. The primary strategy is to develop a live-attenuated virus for intranasal immunization, which is particularly well suited against a respiratory virus. Reverse genetics provides a means of developing highly characterized 'designer' attenuated vaccine candidates. To date, several promising vaccine candidates have been developed, each using a different mode of attenuation. One candidate involves deletion of the G glycoprotein, providing attenuation that is probably based on reduced efficiency of attachment. A second candidate involves deletion of the M2-2 protein, which participates in regulating RNA synthesis and whose deletion has the advantageous property of upregulating transcription and increasing antigen synthesis. A third candidate involves replacing the P protein gene of HMPV with its counterpart from the related avian metapneumovirus, thereby introducing attenuation owing to its chimeric nature and host range restriction. Another live vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine. Additional modifications to provide improved vaccines will also be discussed.

Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine?

PubMed

Evans, Jennifer S; Horton, Daniel L; Easton, Andrew J; Fooks, Anthony R; Banyard, Ashley C

2012-12-14

All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Evolution of the Sabin Vaccine into Pathogenic Derivatives without Appreciable Changes in Antigenic Properties: Need for Improvement of Current Poliovirus Surveillance▿

PubMed Central

Yakovenko, Maria L.; Korotkova, Ekaterina A.; Ivanova, Olga E.; Eremeeva, Tatyana P.; Samoilovich, Elena; Uhova, Iryna; Gavrilin, Gene V.; Agol, Vadim I.

2009-01-01

The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with “Sabin-like” properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV. PMID:19129444

Genetic heterogeneity of L-Zagreb mumps virus vaccine strain.

PubMed

Kosutic-Gulija, Tanja; Forcic, Dubravko; Santak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata

2008-07-10

The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.

A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

PubMed

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-04-01

Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

Toward Novel Vaccines Against Tuberculosis: Current Hopes and Obstacles

PubMed Central

Thaiss, Christoph A.; Kaufmann, Stefan H.E.

2010-01-01

Approximately 2 million people die of tuberculosis (TB) each year. The current vaccine, Bacille Calmette-Guérin (BCG), albeit widely employed, does not protect against adult pulmonary disease, and new vaccines are urgently needed to reduce the incidence of TB worldwide. New insights into the cellular and molecular mechanisms that underlie the interactions between Mycobacterium tuberculosis and its host have been exploited to develop novel vaccine candidates that recently have entered clinical trials. This review provides a brief overview of different approaches toward a new vaccination strategy and summarizes major challenges for the next decade. PMID:21165340

Vaccines against malaria.

PubMed

Ouattara, Amed; Laurens, Matthew B

2015-03-15

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Challenges of influenza A viruses in humans and animals and current animal vaccines as an effective control measure

PubMed Central

2018-01-01

Influenza A viruses (IAVs) are genetically diverse and variable pathogens that share various hosts including human, swine, and domestic poultry. Interspecies and intercontinental viral spreads make the ecology of IAV more complex. Beside endemic IAV infections, human has been exposed to pandemic and zoonotic threats from avian and swine influenza viruses. Animal health also has been threatened by high pathogenic avian influenza viruses (in domestic poultry) and reverse zoonosis (in swine). Considering its dynamic interplay between species, prevention and control against IAV should be conducted effectively in both humans and animal sectors. Vaccination is one of the most efficient tools against IAV. Numerous vaccines against animal IAVs have been developed by a variety of vaccine technologies and some of them are currently commercially available. We summarize several challenges in control of IAVs faced by human and animals and discuss IAV vaccines for animal use with those application in susceptible populations. PMID:29399575

Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

NASA Astrophysics Data System (ADS)

Liu, Jun

2009-04-01

Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

Genetic appraisal of serological response post vaccination against enterotoxaemia (ET) in Malpura and Avikalin sheep.

PubMed

Gowane, G R; Akram, Najif; Prince, L L L; Prakash, Ved; Kumar, Arun

2017-04-01

Enterotoxaemia (ET) is a fatal enteric disease of small ruminants attributable to a toxigenic type of Clostridium perfringens. The key strategy for prevention of ET is the management and vaccination. Present study aimed at identifying the sources of variation for ET vaccine response especially against epsilon toxin in 173 sheep that included 83 Avikalin and 90 Malpura lambs raised at the institute flock in the semi-arid region of India. The mean age at vaccination was 90 days. Sera were tested by blocking ELISA. Study showed significant variability for response to ET vaccine. 5.2% animals had + positivity, 20.8% animals had ++ positivity, 51.4% animals had +++ positivity and 22.5% animals had ++++ positivity. Amongst environmental determinants, breed, season, sex and age at vaccination proved to be non-significant sources of variation (P > 0.05). MHC genotypes with DRB1 gene and DQA2 genes also revealed non-significant association with ET vaccine response; however, a trend of decreasing PI values with increasing ranks was observed. Study revealed strong response of epsilon toxin along with complexity of the ET vaccine response as phenotype to be explained by genetic and non-genetic factors. The importance of better management practices and vaccination is suggested for preventive measures.

Genetic heterogeneity of L-Zagreb mumps virus vaccine strain

PubMed Central

Kosutic-Gulija, Tanja; Forcic, Dubravko; Šantak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata

2008-01-01

Background The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes. PMID:18616793

Licensed pertussis vaccines in the United States. History and current state.

PubMed

Klein, Nicola P

2014-01-01

The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

Military vaccines in today's environment.

PubMed

Schmaljohn, Connie S; Smith, Leonard A; Friedlander, Arthur M

2012-08-01

The US military has a long and highly distinguished record of developing effective vaccines against pathogens that threaten the armed forces. Many of these vaccines have also been of significant benefit to civilian populations around the world. The current requirements for force protection include vaccines against endemic disease threats as well as against biological warfare or bioterrorism agents, to include novel or genetically engineered threats. The cost of vaccine development and the modern regulatory requirements for licensing vaccines have strained the ability of the program to maintain this broad mission. Without innovative vaccine technologies, streamlined regulatory strategies, and coordinating efforts for use in civilian populations where appropriate, the military vaccine development program is in jeopardy.

Current State in the Development of Candidate Therapeutic HPV Vaccines

PubMed Central

Yang, Andrew; Jeang, Jessica; Cheng, Kevin; Cheng, Ting; Yang, Benjamin; Wu, T.-C.; Hung, Chien-Fu

2016-01-01

Summary The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID:26901118

Correlation of genetic variability with safety of mumps vaccine Urabe AM9 strain.

PubMed

Amexis, G; Fineschi, N; Chumakov, K

2001-08-15

The Urabe AM9 strain of mumps vaccine live is known for its genetic instability and some vaccines derived from this strain were withdrawn from the market due to an excessive number of vaccine-associated parotitis and meningitis cases. To identify the molecular basis of this instability, we determined complete nucleotide sequences of several stocks of the Urabe strain used for vaccine production by different manufacturers and of two clinical isolates from cases of vaccine-associated meningitis. In contrast to previously published studies relating the Lys335 --> Glu mutation in the viral HN gene with neurovirulence of mumps virus, we could not confirm any association of this mutation with the safety of mumps vaccine. Each of the three vaccine stocks studied had its own characteristic profile of mutations that was identified by cDNA sequencing and quantitated by mutant analysis by PCR and restriction enzyme cleavage. Determination of the mutational profile of mumps vaccine lots could allow vaccine manufacturers to characterize seed viruses and monitor the consistency of vaccine production to prevent emergence of virulent revertants.

New Generation Live Vaccines against Human Respiratory Syncytial Virus Designed by Reverse Genetics

PubMed Central

Collins, Peter L.; Murphy, Brian R.

2005-01-01

Development of a live pediatric vaccine against human respiratory syncytial virus (RSV) is complicated by the need to immunize young infants and the difficulty in balancing attenuation and immunogenicity. The ability to introduce desired mutations into infectious virus by reverse genetics provides a method for identifying and designing highly defined attenuating mutations. These can be introduced in combinations as desired to achieve gradations of attenuation. Attenuation is based on several strategies: multiple independent temperature-sensitive point mutations in the polymerase, a temperature-sensitive point mutation in a transcription signal, a set of non–temperature-sensitive mutations involving several genes, deletion of a viral RNA synthesis regulatory protein, and deletion of viral IFN α/β antagonists. The genetic stability of the live vaccine can be increased by judicious choice of mutations. The virus also can be engineered to increase the level of expression of the protective antigens. Protective antigens from antigenically distinct RSV strains can be added or swapped to increase the breadth of coverage. Alternatively, the major RSV protective antigens can be expressed from transcription units added to an attenuated parainfluenza vaccine virus, making a bivalent vaccine. This would obviate the difficulties inherent in the fragility and inefficient in vitro growth of RSV, simplifying vaccine design and use. PMID:16113487

A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

PubMed Central

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-01-01

Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. PMID:25884628

Current issues in the economics of vaccination against dengue.

PubMed

Tozan, Yesim

2016-01-01

Dengue is a major public health concern in tropical and subtropical areas of the world. The prospects for dengue prevention have recently improved with the results of efficacy trials of a tetravalent dengue vaccine. Although partially effective, once licensed, its introduction can be a public health priority in heavily affected countries because of the perceived public health importance of dengue. This review explores the most immediate economic considerations of introducing a new dengue vaccine and evaluates the published economic analyses of dengue vaccination. Findings indicate that the current economic evidence base is of limited utility to support country-level decisions on dengue vaccine introduction. There are a handful of published cost-effectiveness studies and no country-specific costing studies to project the full resource requirements of dengue vaccine introduction. Country-level analytical expertise in economic analyses, another gap identified, needs to be strengthened to facilitate evidence-based decision-making on dengue vaccine introduction in endemic countries.

Primary vaccine failure to routine vaccines: Why and what to do?

PubMed

Wiedermann, Ursula; Garner-Spitzer, Erika; Wagner, Angelika

2016-01-01

There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.

Vaccination and allergy.

PubMed

Rottem, Menachem; Shoenfeld, Yehuda

2004-06-01

Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks. Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations. Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

Brucellosis vaccines for livestock.

PubMed

Goodwin, Zakia I; Pascual, David W

2016-11-15

Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination, and Safety

NASA Astrophysics Data System (ADS)

Moss, Bernard

1996-10-01

Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure--function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

Current challenges in the development of vaccines for pneumonic plague

PubMed Central

Smiley, Stephen T

2008-01-01

Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

[Influenza vaccination. Effectiveness of current vaccines and future challenges].

PubMed

Ortiz de Lejarazu, Raúl; Tamames, Sonia

2015-01-01

Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys

PubMed Central

Letvin, Norman L.; Rao, Srinivas S.; Montefiori, David C.; Seaman, Michael S.; Sun, Yue; Lim, So-Yon; Yeh, Wendy W.; Asmal, Mohammed; Gelman, Rebecca S.; Shen, Ling; Whitney, James B.; Seoighe, Cathal; Lacerda, Miguel; Keating, Sheila; Norris, Philip J.; Hudgens, Michael G.; Gilbert, Peter B.; Buzby, Adam P.; Mach, Linh V.; Zhang, Jinrong; Balachandran, Harikrishnan; Shaw, George M.; Schmidt, Stephen D.; Todd, John-Paul; Dodson, Alan; Mascola, John R.; Nabel, Gary J.

2013-01-01

The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was an about one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01–negative monkeys challenged with SIVsmE660, no CD8+ T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4+ T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanism of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies. PMID:21543722

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys.

PubMed

Letvin, Norman L; Rao, Srinivas S; Montefiori, David C; Seaman, Michael S; Sun, Yue; Lim, So-Yon; Yeh, Wendy W; Asmal, Mohammed; Gelman, Rebecca S; Shen, Ling; Whitney, James B; Seoighe, Cathal; Lacerda, Miguel; Keating, Sheila; Norris, Philip J; Hudgens, Michael G; Gilbert, Peter B; Buzby, Adam P; Mach, Linh V; Zhang, Jinrong; Balachandran, Harikrishnan; Shaw, George M; Schmidt, Stephen D; Todd, John-Paul; Dodson, Alan; Mascola, John R; Nabel, Gary J

2011-05-04

The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01-negative monkeys challenged with SIVsmE660, no CD8(+) T cell response or innate immune response was associated with protection against virus acquisition. However, low levels of neutralizing antibodies and an envelope-specific CD4(+) T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at least one permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlights the need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies.

Vaccines for pandemic influenza. The history of our current vaccines, their limitations and the requirements to deal with a pandemic threat.

PubMed

Hampson, Alan W

2008-06-01

Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic. The bulk of current vaccines are inactivated split virus vaccines produced from egg-grown virus and have only modest improvements compared with those first introduced over 60 years ago. Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically naïve recipients. The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity. There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic. New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.

Cost Effectiveness of a Shingles Vaccine Booster for Currently Vaccinated Adults in the U.S.

PubMed

Le, Phuc; Rothberg, Michael B

2017-12-01

The Advisory Committee on Immunization Practices recommends a single dose of the live attenuated herpes zoster vaccine in people aged ≥60 years. Because vaccine-induced protection decreases to zero after 10 years, many vaccinated people will soon be subject to an increased risk of the disease. The study objective was to determine the cost effectiveness of a herpes zoster vaccine booster and its optimal timing among immunocompetent adults first vaccinated at aged ≥60 years. A Markov model was built to follow vaccinated individuals for a lifetime. From the societal perspective, costs and quality-adjusted life years were compared between no booster versus booster options. A booster was given any time between 1 and 20 years after the first dose, and for those who had the first dose at different ages: 60, 70, and 80 years. Because people entered the model already vaccinated, costs and side effects of the first dose were not included. The booster was assumed to have the same efficacy and waning rate as the initial vaccination. Model inputs were based on published literature. A cost effectiveness threshold of $100,000/quality-adjusted life year was used. The analysis was conducted in 2016. Cost effectiveness of a booster varied by age and time since vaccination. The booster cost <$100,000/quality-adjusted life year if given >5 years after the initial dose, but was most cost effective at around 10 years. The finding was robust to wide variations in model inputs. Under current assumptions, a booster dose of herpes zoster vaccine would be cost effective for all vaccinated people 10 years after initial vaccination. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Neurovirulence safety testing of mumps vaccines--historical perspective and current status.

PubMed

Rubin, S A; Afzal, M A

2011-04-05

Many live, attenuated viral vaccines are derived from wild type viruses with known neurovirulent properties. To assure the absence of residual neurotoxicity, pre-clinical neurovirulence safety testing of candidate vaccines is performed. For mumps virus, a highly neurotropic virus, neurovirulence safety testing is performed in monkeys. However, laboratory studies suggest an inability of this test to correctly discern among virus strains of varying neurovirulence potential in man, and, further, some vaccines found to be neuroattenuated in monkeys were later found to be neurovirulent in humans when administered in large numbers. Over the past decade, concerted efforts have been made to replace monkey-based neurovirulence safety testing with more informative, alternative methods. This review summarizes the current status of mumps vaccine neurovirulence safety testing and insights into models currently approved and those under development. Published by Elsevier Ltd.

Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

PubMed

Billeter, M A; Naim, H Y; Udem, S A

2009-01-01

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

Human papillomavirus vaccines: current status and future prospects.

PubMed

Garland, Suzanne M; Smith, Jennifer S

2010-06-18

Worldwide, cervical cancer is the second most common cancer of women. Less-developed countries bear the greatest burden in terms of morbidity and mortality, largely due to the lack of organized screening programmes. Cervical cancer is the first cancer shown to be caused solely by virological agents: oncogenic genotypes of human papillomavirus (HPV). Two recently developed prophylactic cervical cancer vaccines, which are based on viral-like particle (VLP) technology of HPV, have the capacity to diminish a large proportion of cervical cancer cases worldwide. However, to be successful public health tools, they need to be widely implemented to the appropriate target population, preferably prior to first sexual intercourse. To increase vaccination coverage, national programmes in some countries have also included catch-up vaccination, for a limited time period, to young adult women aged up to 26 years. Despite the excellent efficacy for high-grade dysplasia due to vaccine-related HPV types (near to 100%) and immunogenicity induced against the HPV types 16 and 18 in females naive to those HPV types pre-vaccination, some form of cervical precancer screening will still be necessary. Immunity to HPV is primarily type specific, and thus protection induced by the current generation of vaccines, based on a limited number of HPV VLP types, cannot provide complete protection against all oncogenic HPV types. Both these vaccines translate to protection of cervical cancer in the order of 70-75%, which represents the percentage of invasive cancers attributable to HPV-16 and -18. Challenges to ensuring the successful control of this largely preventable disease include endorsement by governments and policy makers, affordable prices, education at all levels, overcoming barriers to vaccination and continued adherence to screening programmes.

[Infection prevention in newborns through maternal vaccination: current insights and developments].

PubMed

van der Maas, N A T; van Aerde, K; Bont, L J; Bekker, M N; Rots, N; de Melker, H E

2016-01-01

- In the first few months of life, newborns are vulnerable to infections.- Vaccination of the pregnant mother leads to transplacental antibody transfer, resulting in the best possible protection of the newborn.- Maternal vaccination has long been given for the prevention of tetanus in developing countries, and for the prevention of pertussis and influenza in developed countries, such as the United States, England and Belgium. These vaccinations give newborns good protection and, to date, no adverse effects are known for the foetus or the pregnancy.- Currently, phase 3 trials during pregnancy are ongoing following maternal vaccination against group B streptococci and respiratory syncytial virus. Here, again, no risks to mother or child have been reported.- Recently, the Dutch Health Council advised that all pregnant women in the Netherlands be vaccinated against pertussis in a vaccination programme.- This paper gives an overview of effectiveness, safety and practicalities of maternal vaccination.

Traditional and New Influenza Vaccines

PubMed Central

Wong, Sook-San

2013-01-01

SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

The current status, challenges, and future developments of new tuberculosis vaccines.

PubMed

Gong, Wenping; Liang, Yan; Wu, Xueqiong

2018-03-30

Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10 causes of death worldwide. TB results in more fatalities than multi-drug resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the prevention and control of infectious diseases. Unfortunately, the only licensed preventive vaccine against TB, bacilli Calmette-Guérin (BCG), is ineffective for prevention of pulmonary TB in adults. Therefore, it is very important to develop novel vaccines for TB prevention and control. This literature review provides an overview of the innate and adaptive immune response during M. tuberculosis infection, and presents current developments and challenges to novel TB vaccines. A comprehensive understanding of vaccines in preclinical and clinical studies provides extensive insight for the development of safer and more efficient vaccines, and may inspire new ideas for TB prevention and treatment.

IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

PubMed Central

Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

2016-01-01

Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers. PMID:27019828

Ebola hemorrhagic Fever and the current state of vaccine development.

PubMed

Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

2014-12-01

Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

Vaccines for bovine neosporosis: current status and key aspects for development.

PubMed

Horcajo, P; Regidor-Cerrillo, J; Aguado-Martínez, A; Hemphill, A; Ortega-Mora, L M

2016-12-01

Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major economic losses associated with the disease. Currently, there is no treatment or vaccine available against abortion or transmission caused by Neospora caninum infection in cattle. However, vaccination is considered the best measure of control against bovine neosporosis. Several host and parasite factors can influence the dynamics of the infection in bovines. Moreover, the availability of well-defined infection models is a key factor for the evaluation of vaccine candidates. However, working with cattle is not easy due to difficult handling, facilities and costs, and therefore, 'more affordable' models could be used for screening of promising vaccines to establish proof of concept. So far, live-attenuated vaccines have shown good efficacy against exogenous transplacental transmission; however, they have relevant disadvantages and associated risks, which render inactivated or subunit vaccines the best way forward. The identification of novel potential targets and vaccines, and the application of innovative vaccine technologies in harmonized experimental animal models, will accelerate the development of an effective vaccine against bovine neosporosis. © 2016 John Wiley & Sons Ltd.

Genetic Variation among Plasmodium vivax Isolates Adapted to Non-Human Primates and the Implication for Vaccine Development

PubMed Central

Ntumngia, Francis B.; McHenry, Amy M.; Barnwel, John W.; Cole-Tobian, Jennifer; King, Christopher L.; Adams, John H.

2009-01-01

Plasmodium vivax Duffy binding protein (DBP) is vital for parasite development, thereby making this molecule a good vaccine candidate. Preclinical development of a P. vivax vaccine often involves use of primate models prior to testing efficacy in humans, but primate isolates are poorly characterized. We analyzed the complete gene coding for the DBP in several P. vivax isolates that are used for experimental primate infections and compared these sequences with the Salvador I DBP isolate, which is being used for vaccine development. Our results affirm that primate-adapted isolates are genetically similar to P. vivax circulating in humans, but variability is greatest in the putative target of protective antibodies. In addition, some P. vivax isolates contain multiple genetically different clones. Testing a DBP vaccine may therefore be complicated by heterogeneity and diversity of the P. vivax isolates available for in vivo challenge. PMID:19190217

Virus vaccines: principles and prospects.

PubMed Central

Melnick, J. L.

1989-01-01

The present status of vaccination for controlling viral diseases is reviewed, and the needs and directions for future investigations are discussed. A survey of viral vaccines now in use has shown that knowledge about the viral agents and about the hosts' responses to infection was essential for their development. The steps needed to demonstrate the efficacy and safety of a viral vaccine are summarized; the final requirement for a successful vaccine is that it be administered in proper dosage and potency to the target populations. After general remarks on the proper use of current vaccines there follows an overview of various developments in creating new vaccines, along with the predicted time-frames for their coming into general use. Topics considered include vaccines to be administered locally at the portal of entry, subunit vaccines, viruses attenuated by genetic manipulation, use of viral vectors, vaccines developed by means of recombinant DNA, synthetic peptides, and anti-idiotype vaccines, as well as new vaccines being developed by more conventional methods. PMID:2663217

Live attenuated vaccines: Historical successes and current challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minor, Philip D., E-mail: Philip.Minor@nibsc.org

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up inmore » clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.« less

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

PubMed

Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

2015-01-01

Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Vaccine-derived polioviruses.

PubMed

Agol, Vadim I

2006-06-01

The Sabin oral poliovaccine (OPV) is extremely efficacious and safe, despite its inherent genetic instability. While reversion to nearly wild-type phenotype regularly occurs soon after the onset of OPV reproduction in the gastro-intestinal tract of vaccine recipients or their contacts, this is usually not a big problem, provided the vaccine is used either for mass vaccination or in populations with a relatively high level of anti-polio immunity. However, if these conditions are not met, the vaccine viruses are likely to be converted into highly transmissible agents with a nearly wild-type level of neurovirulence. Moreover, OPV viruses may persist and evolve even in adequately immunized populations. The current strategy for the "endgame" of poliovirus eradication envisions cessation of OPV usage shortly after the last isolation of a wild poliovirus. If implemented, this strategy would result in rapid growth of non-immune human populations at the time when OPV derivatives would very likely be persisting. Therefore, the planned cessation of OPV vaccination is associated with a very high, and in the author's opinion, unacceptable risk of polio outbreaks caused by OPV derivatives. The only currently available tool to curb such outbreaks is OPV, which should have been used at a global scale. Safe discontinuation of OPV vaccination will be possible only after an efficient new vaccine or an anti-poliovirus drug is available. To achieve this goal, stimulation of poliovirus research and elimination of organizational and financial obstacles preventing it are needed.

Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

PubMed

Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

2015-10-13

Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

PubMed

Haber, Penina; Moro, Pedro L; Ng, Carmen; Lewis, Paige W; Hibbs, Beth; Schillie, Sarah F; Nelson, Noele P; Li, Rongxia; Stewart, Brock; Cano, Maria V

2018-01-25

Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education

Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

PubMed

Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

2016-09-07

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rhabdoviruses as vaccine platforms for infectious disease and cancer.

PubMed

Zemp, Franz; Rajwani, Jahanara; Mahoney, Douglas J

2018-05-21

The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV members are being developed as live-attenuated vaccine vectors for the prevention or treatment of infectious disease and cancer. These include the prototype recombinant Vesicular Stomatitis Virus (rVSV) and the more recently developed recombinant Maraba Virus, both species within the genus Vesiculoviridae. A relatively strong safety profile in humans, robust immunogenicity and genetic malleability are key features that make the RV family attractive vaccine platforms. Currently, the rVSV vector is in preclinical development for vaccination against numerous high-priority infectious diseases, with clinical evaluation underway for HIV/AIDS and Ebola virus disease. Indeed, the success of the rVSV-ZEBOV vaccine during the 2014-15 Ebola virus outbreak in West Africa highlights the therapeutic potential of rVSV as a vaccine vector for acute, life-threatening viral illnesses. The rVSV and rMaraba platforms are also being tested as 'oncolytic' cancer vaccines in a series of phase 1-2 clinical trials, after being proven effective at eliciting immune-mediated tumour regression in preclinical mouse models. In this review, we discuss the biological and genetic features that make RVs attractive vaccine platforms and the development and ongoing testing of rVSV and rMaraba strains as vaccine vectors for infectious disease and cancer.

Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains

PubMed Central

Bari, Fufa D.; Parida, Satya; Tekleghiorghis, Tesfaalem; Dekker, Aldo; Sangula, Abraham; Reeve, Richard; Haydon, Daniel T.; Paton, David J.; Mahapatra, Mana

2014-01-01

Vaccine strain selection for emerging foot-and-mouth disease virus (FMDV) outbreaks in enzootic countries can be addressed through antigenic and genetic characterisation of recently circulating viruses. A total of 56 serotype A FMDVs isolated between 1998 and 2012, from Central, East and North African countries were characterised antigenically by virus neutralisation test using antisera to three existing and four candidate vaccine strains and, genetically by characterising the full capsid sequence data. A Bayesian analysis of the capsid sequence data revealed the viruses to be of either African or Asian topotypes with subdivision of the African topotype viruses into four genotypes (Genotypes I, II, IV and VII). The existing vaccine strains were found to be least cross-reactive (good matches observed for only 5.4–46.4% of the sampled viruses). Three bovine antisera, raised against A-EA-2007, A-EA-1981 and A-EA-1984 viruses, exhibited broad cross-neutralisation, towards more than 85% of the circulating viruses. Of the three vaccines, A-EA-2007 was the best showing more than 90% in-vitro cross-protection, as well as being the most recent amongst the vaccine strains used in this study. It therefore appears antigenically suitable as a vaccine strain to be used in the region in FMD control programmes. PMID:25171846

Prospects for new viral vaccines.

PubMed

Marmion, B P

1980-08-11

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

The future of human DNA vaccines

PubMed Central

Li, Lei; Saade, Fadi; Petrovsky, Nikolai

2012-01-01

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including “epigenetics” and “omics” approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans PMID:22981627

The future of human DNA vaccines.

PubMed

Li, Lei; Saade, Fadi; Petrovsky, Nikolai

2012-12-31

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including "epigenetics" and "omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

[Rubella virus genetic determinant of attenuation].

PubMed

Dmitriev, G V; Borisova, T K; Faizuloev, E B; Desiatskova, R G; Zverev, V V

2014-01-01

Vaccination is the most effective and available way to prevent Rubella. Presently, 9 vaccine strains were registered. Nevertheless, the molecular mechanisms of the attenuation were poorly elucidated for the rubella virus. However, the study of these mechanisms identifying genotypic and phenotypic markers of attenuation, which together with sequence analysis could be used for the genetic stability control of vaccine strains, is still of current interest. Common trends of genetic changes in the process of adaptation to cold were found due to comparison of nucleic acid and amino acid sequences of the Russian strain C-77 with corresponding positions of the known rubella virus strains and its wild type progenitors, if available.

Primary Care Physicians' Struggle with Current Adult Pneumococcal Vaccine Recommendations.

PubMed

Hurley, Laura P; Allison, Mandy A; Pilishvili, Tamara; O'Leary, Sean T; Crane, Lori A; Brtnikova, Michaela; Beaty, Brenda L; Lindley, Megan C; Bridges, Carolyn B; Kempe, Allison

2018-01-01

In 2012, the Advisory Committee on Immunization Practices recommended 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for at-risk adults ≥19; in 2014, it expanded this recommendation to adults ≥65. Primary care physicians' practice, knowledge, attitudes, and beliefs regarding these recommendations are unknown. Primary care physicians throughout the U.S. were surveyed by E-mail and post from December 2015 to January 2016. Response rate was 66% (617 of 935). Over 95% of respondents reported routinely assessing adults' vaccination status and recommending both vaccines. A majority found the current recommendations to be clear (50% "very clear," 38% "somewhat clear"). Twenty percent found the upfront cost of purchasing PCV13, lack of insurance coverage, inadequate reimbursement, and difficulty determining vaccination history to be "major barriers" to giving these vaccines. Knowledge of recommendations varied, with 83% identifying the PCV13 recommendation for adults ≥65 and only 21% identifying the recommended interval between PCV13 and PPSV23 in an individual <65 at increased risk. Almost all surveyed physicians reported recommending both pneumococcal vaccines, but a disconnect seems to exist between perceived clarity and knowledge of the recommendations. Optimal implementation of these recommendations will require addressing knowledge gaps and reported barriers. © Copyright 2018 by the American Board of Family Medicine.

Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines.

PubMed

Zuckerman, Jane N; Hatz, Christoph; Kantele, Anu

2017-10-01

Typhoid and paratyphoid fever remain a global health problem, which - in non-endemic countries - are mainly seen in travelers, particularly in VFRs (visiting friends and relatives), with occasional local outbreaks occurring. A rise in anti-microbial resistance emphasizes the role of preventive measures, especially vaccinations against typhoid and paratyphoid fever for travelers visiting endemic countries. Areas covered: This state-of-the-art review recapitulates the epidemiology and mechanisms of disease of typhoid and paratyphoid fever, depicts the perspective of non-endemic countries and travelers (VFRs), and collectively presents current European recommendations for typhoid fever vaccination. We provide a brief overview of available (and developmental) vaccines in Europe, present current data on cross-protection to S. Paratyphi, and aim to provide a background for typhoid vaccine decision-making in travelers. Expert commentary: European recommendations are not harmonized. Experts must assess vaccination of travelers based on current country-specific recommendations. Travel health practitioners should be aware of the issues surrounding vaccination of travelers and be motivated to increase awareness of typhoid and paratyphoid fever risks.

Antigenic and genetic comparison of foot-and-mouth disease virus serotype O Indian vaccine strain, O/IND/R2/75 against currently circulating viruses.

PubMed

Mahapatra, Mana; Yuvaraj, S; Madhanmohan, M; Subramaniam, S; Pattnaik, B; Paton, D J; Srinivasan, V A; Parida, Satya

2015-01-29

Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East-South Asia (ME-SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antigenic and genetic comparison of foot-and-mouth disease virus serotype O Indian vaccine strain, O/IND/R2/75 against currently circulating viruses

PubMed Central

Mahapatra, Mana; Yuvaraj, S.; Madhanmohan, M.; Subramaniam, S.; Pattnaik, B.; Paton, D.J.; Srinivasan, V.A.; Parida, Satya

2015-01-01

Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East–South Asia (ME–SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences. PMID:25500306

Antigenic analysis of genetic variants of Canine distemper virus.

PubMed

Anis, Eman; Holford, Amy L; Galyon, Gina D; Wilkes, Rebecca P

2018-06-01

Canine distemper virus (CDV) is an RNA virus of the genus Morbillivirus within the family Paramyxoviridae. CDV produces multi-systemic disease in dogs and other terrestrial carnivores. With the development of modified live vaccines in the 1950s and 1960s, the disease, with a few exceptions, has been successfully controlled. However, recently the cases of CDV in vaccinated dogs have been increasing throughout the world, including the United States. There are many reasons that can lead to vaccine failure, including antigenic differences between the vaccine strains and the currently circulating wild-type strains. Currently, there are at least three genetically different CDV lineages circulating in the US. Therefore, in this study, we evaluated various wild-type CDV and vaccine isolates to determine if the genetic differences observed among various strains result in significant antigenic differences based on changes to the neutralizing epitopes. The results of a cross-neutralization assay revealed that there are antigenic differences among the tested CDV wild-type isolates as well as between the tested isolates and the vaccine strains currently used in the US. Therefore, these results suggest the need to develop an updated CDV vaccine. Copyright © 2018 Elsevier B.V. All rights reserved.

Complement evasion by Bordetella pertussis: implications for improving current vaccines.

PubMed

Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

2015-04-01

Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

PubMed

van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

2009-12-15

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

Current status of production and market of human vaccine products in Korea.

PubMed

Kim, So Youn; Cho, Jahyang; Cha, Sung-Ho; Bae, Chong-Woo

2013-07-01

The goal of this study was to build basic information related to the production and market of human vaccine products in Korea, which can be an important indicator to provide basic data in practical use. Statistical data were obtained from the Bank of Korea, Korea Health Industry Development Institute, Korea Pharmaceutical Traders Association, and Korea Pharmaceutical Manufacturers Association. Vaccines are the 10th ranked drugs in the classification of whole complete preparated drugs. The production output of vaccines in Korea was 392.2 billion KRW in 2011, comprising 2.83% of complete preparated drug production output (13 trillion 880.8 billion KRW) and 2.54% of medical-pharmaceutical product output (15 trillion 440.3 billion KRW). The market scale of vaccines in Korea was 710 billion KRW in 2011, with an annual average growth rate of 11% in the past 6 years, comprising 2% of vaccine market in the world. There was also a significant increase in essential vaccines and other preventive vaccines in a global scale. Vaccines have the potential of becoming an emerging attractive industry. Based on the current analysis about the production of vaccine products and market scale, further development of the vaccine industry is expected in Korea.

When gene medication is also genetic modification--regulating DNA treatment.

PubMed

Foss, Grethe S; Rogne, Sissel

2007-07-26

The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

Influenza A virus vaccines for swine.

PubMed

Vincent, Amy L; Perez, Daniel R; Rajao, Daniela; Anderson, Tavis K; Abente, Eugenio J; Walia, Rasna R; Lewis, Nicola S

2017-07-01

Economic losses due to influenza A virus (IAV) infections are substantial and a global problem, ranking among the top three major health challenges in the swine industry. Currently, H1 and H3 subtypes circulate in pigs globally associated with different combinations of N1 and N2 subtypes; however, the origin, gene constellation, and antigenic makeup of IAV vary greatly on different continents. Vaccination is one means of mitigating the effects of IAV disease, and vaccines are most effective if the strains included closely match the currently circulating strains in pigs. Genetic analyses provide panoramic views of the virus landscape at the sequence level and, thus, can aid in the selection of well-matched swine IAV vaccine strains, but is not sufficient alone. Additionally, a major challenge in selecting appropriate swine IAV vaccine strains is the co-circulation of multiple lineages of viruses in the same region, requiring multivalent or broadly cross-reacting antigens. Due to this complex IAV ecology in swine, new vaccination strategies and vaccine platforms are needed. The hemagglutinin (HA) viral protein is the major target of neutralizing antibodies, which are widely considered to be correlated with protection. Virus variants that are not recognized by previously elicited antibodies can render traditional vaccines that primarily elicit humoral responses ineffective, and therefore result in the need for vaccine strain reformulation and re-vaccination. In the future, new vaccine platforms may be on the market that will provide alternative options to those currently available. Nonetheless, a collaborative approach is needed to improve IAV vaccine strain selection for use in swine. Published by Elsevier B.V.

Development of whole sporozoite malaria vaccines.

PubMed

Hollingdale, Michael R; Sedegah, Martha

2017-01-01

Despite recent advances, malaria remains a major health threat both to populations in endemic areas as well travelers, including military personnel, to these areas. Subunit vaccines have not yet achieved sufficient efficacy needed for use in any of these at risk populations. Areas covered: This review discusses the current status of various whole sporozoite vaccine approaches and is mainly focused on current clinical trials. Expert commentary: Nearly 100% efficacy was achieved by administering multiple bites of radiation-attenuated sporozoite (RAS) Plasmodium falciparum-infected mosquitoes; this is impractical for widespread use. Now, this high level efficacy has been reproduced using purified, metabolically active RAS (PfSPZ Sanaria® Vaccine), which is undergoing extensive clinical testing. Alternative whole sporozoite vaccines include immunization with fully infectious sporozoites under chloroquine prophylaxis (CPS) or as genetically-attenuated parasites (GAP). By also manufacturing purified infectious sporozoites, it is now possible to combine these with CPS and GAP, as well as perform challenge studies using controlled doses of sporozoites.

Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design.

PubMed

Kazi, Ada; Chuah, Candy; Majeed, Abu Bakar Abdul; Leow, Chiuan Herng; Lim, Boon Huat; Leow, Chiuan Yee

2018-03-12

Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.

Circulating vaccine-derived polioviruses: current state of knowledge.

PubMed Central

Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

2004-01-01

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination.

PubMed

Lindesmith, Lisa C; Mallory, Michael L; Jones, Taylor A; Richardson, Charles; Goodwin, Robert R; Baehner, Frank; Mendelman, Paul M; Bargatze, Robert F; Baric, Ralph S

2017-03-15

Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves. Blockade Ab avidity to the GI.1 vaccine component peaked at day 35 (7 days after dose 2). Avidities to heterotypic genogroup I VLPs were not sustained at day 35 after vaccination or GI.1 infection, as measured from archived sera. Only secretor-positive participants maintained high avidity blockade Ab to GI.1 at day 180. Avidity to the GII.4c vaccine component peaked at day 7, remained elevated through day 180, and was not secretor dependent. Avidity to an immunologically novel GII.4 strain VLP correlated with preexisting Ab titer to an ancestral strain Epitope A. Host genetics and pre-exposure history shape norovirus vaccine Ab responses, including blockade Ab avidity. Avidity of potentially neutralizing Ab may be an important metric for evaluating vaccine responses to highly penetrant viruses with cross-reactive serotypes. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

[Vaccine application of recombinant herpesviruses].

PubMed

Yokoyama, N; Xuan, X; Mikami, T

2000-04-01

Recently, genetic engineering using recombinant DNA techniques has been applied to design new viral vaccines in order to reduce some problems which the present viral vaccines have. Up to now, many viruses have been investigated for development of recombinant attenuated vaccines or live viral vectors for delivery of foreign genes coding immunogenic antigens. In this article, we introduced the new vaccine strategy using genetically engineered herpesviruses.

The current situation of voluntary vaccination and the factors influencing its coverage among children in Takatsuki, Japan: focus on Hib and pneumococcal vaccines.

PubMed

Tsuda, Yuko; Watanabe, Misuzu; Tanimoto, Yoshimi; Hayashida, Itsushi; Kusabiraki, Toshiyuki; Komiyama, Maki; Kono, Koichi

2015-03-01

This study aimed to understand the current scenario of voluntary vaccination and the factors influencing its coverage among 18-month-old children of Takatsuki City, Japan. Based on 1167 parents responses, we found that voluntary vaccination coverage rates were low when compared with routine vaccination rates. The children who were not the first born of the family and who had young and poorly educated parents were less likely to receive voluntary vaccination. Japanese government-supported vaccines, such as Haemophilus influenzae type b and pneumococcal vaccine, had a higher coverage than the vaccines for which parents had to bear the entire vaccination cost. Furthermore, it was found that mass communication media and family pediatricians were effective means to disseminate voluntary vaccination-related information. We envisage that an active participation of medical professionals, easy access to vaccinations, and mass awareness programs will increase voluntary vaccination coverage in Takatsuki. © 2013 APJPH.

Vaccine-preventable infections in Systemic Lupus Erythematosus

PubMed Central

Murdaca, Giuseppe; Orsi, Andrea; Spanò, Francesca; Faccio, Valeria; Puppo, Francesco; Durando, Paolo; Icardi, Giancarlo; Ansaldi, Filippo

2016-01-01

Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE. PMID:26750996

Human papilloma virus vaccines: Current scenario

PubMed Central

Pandhi, Deepika; Sonthalia, Sidharth

2011-01-01

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9–13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40–60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil® is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9–26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9–26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10–25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines. PMID:22021967

Swine influenza virus vaccines: to change or not to change-that's the question.

PubMed

Van Reeth, Kristien; Ma, Wenjun

2013-01-01

Commercial vaccines currently available against swine influenza virus (SIV) are inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs circulating in Europe and the US, the vaccines for each region are produced locally and contain different strains. Even within a continent, there is no standardization of vaccine strains, and the antigen mass and adjuvants can also differ between different commercial products. Recombinant protein vaccines against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse genetics have been tested in experimental studies, but they have not yet reached the market. In this review, we aim to present a critical analysis of the performance of commercial inactivated and novel generation SIV vaccines in experimental vaccination challenge studies in pigs. We pay special attention to the differences between commercial SIV vaccines and vaccination attitudes in Europe and in North America, to the issue of vaccine strain selection and changes, and to the potential advantages of novel generation vaccines over the traditional killed SIV vaccines.

Adenovirus-based genetic vaccines for biodefense.

PubMed

Boyer, Julie L; Kobinger, Gary; Wilson, James M; Crystal, Ronald G

2005-02-01

The robust host responses elicited against transgenes encoded by (E1-)(E3-) adenovirus (Ad) gene transfer vectors can be used to develop Ad-based vectors as platform technologies for vaccines against potential bioterror pathogens. This review focuses on pathogens of major concern as bioterror agents and why Ad vectors are ideal as anti-bioterror vaccine platforms, providing examples from our laboratories of using Ad vectors as vaccines against potential bioterror pathogens and how Ad vectors can be developed to enhance vaccine efficacy in the bioterror war.

Live bacterial vaccines--a review and identification of potential hazards.

PubMed

Detmer, Ann; Glenting, Jacob

2006-06-23

The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.

Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure

PubMed Central

Le Nouën, Cyril; McCarty, Thomas; Brown, Michael; Smith, Melissa Laird; Lleras, Roberto; Dolan, Michael A.; Mehedi, Masfique; Yang, Lijuan; Luongo, Cindy; Liang, Bo; Munir, Shirin; DiNapoli, Joshua M.; Mueller, Steffen; Wimmer, Eckard; Collins, Peter L.; Buchholz, Ursula J.

2017-01-01

Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (RSV) vaccine candidates in the context of strong selective pressure. Codon pair deoptimized (CPD) versions of RSV were attenuated and temperature-sensitive. During serial passage at progressively increasing temperature, a CPD RSV containing 2,692 synonymous mutations in 9 of 11 ORFs did not lose temperature sensitivity, remained genetically stable, and was restricted at temperatures of 34 °C/35 °C and above. However, a CPD RSV containing 1,378 synonymous mutations solely in the polymerase L ORF quickly lost substantial attenuation. Comprehensive sequence analysis of virus populations identified many different potentially deattenuating mutations in the L ORF as well as, surprisingly, many appearing in other ORFs. Phenotypic analysis revealed that either of two competing mutations in the virus transcription antitermination factor M2-1, outside of the CPD area, substantially reversed defective transcription of the CPD L gene and substantially restored virus fitness in vitro and in case of one of these two mutations, also in vivo. Paradoxically, the introduction into Min L of one mutation each in the M2-1, N, P, and L proteins resulted in a virus with increased attenuation in vivo but increased immunogenicity. Thus, in addition to providing insights on the adaptability of genome-scale deoptimized RNA viruses, stability studies can yield improved synthetic RNA virus vaccine candidates. PMID:28049853

Current experience with school-located influenza vaccination programs in the United States

PubMed Central

Ambrose, Christopher S

2011-01-01

In the United States, all children sic months through 18 years of age are recommended to be vaccinated against influenza annually. However, the existing pediatric immunization infrastructure does not have the capacity to vaccinate a high proportion of children each year. School-located influenza vaccination (SLIV) programs provide an opportunity to immunize large numbers of school-age children. We reviewed the medical literature in order to document the current US experience to benefit future SLIV programs. Published reports or abstracts for 36 SLIV programs were identified, some of which spanned multiple years. The programs immunized between 70–128,228 students. While most programs vaccinated 40–50% of students, coverage ranged from 7–73%. Higher percentages of elementary students were vaccinated compared with middle and high school students. While many programs offered only intranasal vaccine, several programs have successfully used both the intranasal and injectable vaccines. Faculty and staff were immunized in some programs and uptake in this group varied considerably. Students were vaccinated quickly during school hours. Costs, where reported, ranged from approximately $20–27 per dose delivered, including both vaccine and administration costs. The greatest need for future US SLIV program implementation is the development of a financially sustainable model that can be replicated annually on a national scale. PMID:21311217

Measles Vaccine.

PubMed

Griffin, Diane E

2018-03-01

Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

PubMed

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-06-16

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

Genetic targeting of the active transcription factor XBP1s to dendritic cells potentiates vaccine-induced prophylactic and therapeutic antitumor immunity.

PubMed

Tian, Shenghe; Liu, Zuqiang; Donahue, Cara; Falo, Louis D; You, Zhaoyang

2012-02-01

In vivo dendritic cells (DC) targeting is an attractive approach with potential advantages in vaccine efficacy, cost, and availability. Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge. Here, we report that in vivo genetic targeting of the active transcription factor XBP1s to DC (XBP1s/DC) potentiated vaccine-induced prophylactic and therapeutic antitumor immunity in multiple tumor models. This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s. The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function. Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro. XBP1s/DC elevated functional DEC205(+)CD8α(+)DC in the draining lymph nodes (DLN). The data suggest a novel role for XBP1s in modulating DC to potentiate tumor vaccine efficacy via overcoming two major obstacles to tumor vaccines (i.e., T cell hyporesponsiveness against poorly immunologic self/tumor Ag and tumor-associated Treg-mediated suppression) and improving DEC205(+)CD8α(+)DC.

[Development of new vaccines].

PubMed

González-Romo, Fernando; Picazo, Juan J

2015-10-01

Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.

Current strategic thinking for the development of a trivalent alphavirus vaccine for human use.

PubMed

Wolfe, Daniel N; Heppner, D Gray; Gardner, Shea N; Jaing, Crystal; Dupuy, Lesley C; Schmaljohn, Connie S; Carlton, Kevin

2014-09-01

Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. © The American Society of Tropical Medicine and Hygiene.

Efficacy of commercial vaccines against newly emerging avian influenza H5N8 virus in Egypt.

PubMed

Kandeil, Ahmed; Sabir, Jamal S M; Abdelaal, Ahmed; Mattar, Ehab H; El-Taweel, Ahmed N; Sabir, Mumdooh J; Khalil, Ahmed Aly; Webby, Richard; Kayali, Ghazi; Ali, Mohamed A

2018-06-26

The newly emerging, highly pathogenic avian influenza (HPAI) H5N8 virus of clade 2.3.4.4 was recently detected in wild birds and domestic poultry in Egypt in the 2016/2017 winter season. Vaccination based on commercial H5 vaccines is used as an essential control strategy in Egyptian poultry. Here, we studied the efficacy of the eight most common commercial H5 poultry vaccines in the Egyptian market and compared them with an experimental vaccine based on the Egyptian LPAI H5N8 virus that was prepared by using reverse genetics. The experimental vaccine and Re-5 commercial vaccine were able to completely protect chickens and significantly reduce virus shedding. Our results indicate that most of the commercial poultry H5 vaccines used in the present study were ineffective because the seed viruses in these vaccines are genetically distinct from the H5N8 viruses currently circulating in Egypt. Although some of the commercial vaccines protected chickens from mortality, they failed to prevent chickens from shedding the virus. Accordingly, we recommend updating and reinforcing the H5N8 prevention and control strategies in Egypt. The vaccination strategy should be reconsidered based on currently circulating viruses.

Multigenic Control of Measles Vaccine Immunity Mediated by Polymorphisms in Measles Receptor, Innate Pathway, and Cytokine Genes

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; O’Byrne, Megan; Jacobson, Robert M.; Pankratz, V. Shane; Poland, Gregory A.

2012-01-01

Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5,7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses. PMID:22265947

Poultry vaccination directed evolution of H9N2 low pathogenicity avian influenza viruses in Korea.

PubMed

Lee, Dong-Hun; Fusaro, Alice; Song, Chang-Seon; Suarez, David L; Swayne, David E

2016-01-15

Significant economic losses in the poultry industries have resulted from H9N2 low pathogenic avian influenza virus infections across North Africa, the Middle East and Asia. The present study investigated the evolutionary dynamics of H9N2 viruses circulating in Korea from 1996 to 2012. Our analysis of viral population dynamics revealed an increase in genetic diversity between the years 2003 and 2007, corresponding to the spread and diversification of H9N2 viruses into multiple genetic groups (named A and B), followed by a sudden decrease in 2007, which was associated with implementation of vaccination using a Clade A virus. Implementation of the H9N2 vaccination program in Korea has dramatically reduced the diversity of H9N2 virus, and only one sub-lineage of clade B has survived, expanded, and currently circulates in Korea. In addition, the antigenic drift of this new genetic group away from the current vaccine strain suggests the need to update the vaccine seed strain. Published by Elsevier Inc.

Current status of meningococcal group B vaccine candidates: capsular or noncapsular?

PubMed

Diaz Romero, J; Outschoorn, I M

1994-10-01

Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists. Current vaccines, based on the group-specific capsular polysaccharides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of infection in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies. Because of the poor immunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases. Alternatively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs. Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed.

Current status of meningococcal group B vaccine candidates: capsular or noncapsular?

PubMed Central

Diaz Romero, J; Outschoorn, I M

1994-01-01

Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists. Current vaccines, based on the group-specific capsular polysaccharides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of infection in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies. Because of the poor immunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases. Alternatively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs. Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed. PMID:7834605

Genetic and antigenic characterization of serotype O FMD viruses from East Africa for the selection of suitable vaccine strain.

PubMed

Lloyd-Jones, Katie; Mahapatra, Mana; Upadhyaya, Sasmita; Paton, David J; Babu, Aravindh; Hutchings, Geoff; Parida, Satya

2017-12-14

Foot-and-mouth disease (FMD) is endemic in Eastern Africa with circulation of multiple serotypes of the virus in the region. Most of the outbreaks are caused by serotype O followed by serotype A. The lack of concerted FMD control programmes in Africa has provided little incentive for vaccine producers to select vaccines that are tailored to circulating regional isolates creating further negative feedback to deter the introduction of vaccine-based control schemes. In this study a total of 80 serotype O FMD viruses (FMDV) isolated from 1993 to 2012 from East and North Africa were characterized by virus neutralisation tests using bovine antisera to three existing (O/KEN/77/78, O/Manisa and O/PanAsia-2) and three putative (O/EA/2002, O/EA/2009 and O/EA/2010) vaccine strains and by capsid sequencing. Genetically, these viruses were grouped as either of East African origin with subdivision into four topotypes (EA-1, 2, 3 and 4) or of Middle-East South Asian (ME-SA) topotype. The ME-SA topotype viruses were mainly detected in Egypt and Libya reflecting the trade links with the Middle East countries. There was good serological cross-reactivity between the vaccine strains and most of the field isolates analysed, indicating that vaccine selection should not be a major constraint for control of serotype O FMD by vaccination, and that both local and internationally available commercial vaccines could be used. The O/KEN/77/78 vaccine, commonly used in the region, exhibited comparatively lower percent in vitro match against the predominant topotypes (EA-2 and EA-3) circulating in the region whereas O/PanAsia-2 and O/Manisa vaccines revealed broader protection against East African serotype O viruses, even though they genetically belong to the ME-SA topotype. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

DNA and RNA-based vaccines: principles, progress and prospects

PubMed Central

Leitner, Wolfgang W.; Ying, Han; Restifo, Nicholas P.

2007-01-01

DNA vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. Here we review the current understanding of the mechanisms underlying the activities of these new vaccines. We focus on recent strategies designed to enhance their function including the use of immunostimulatory (CpG) sequences, dendritic cells (DC), co-stimulatory molecules and cytokine- and chemokine-adjuvants. Although genetic vaccines have been significantly improved, they may not be sufficiently immunogenic for the therapeutic vaccination of patients with infectious diseases or cancer in clinical trials. One promising approach aimed at dramatically increasing the immunogenicity of genetic vaccines involves making them ‘self-replicating’. This can be accomplished by using a gene encoding RNA replicase, a polyprotein derived from alphaviruses, such as Sindbis virus. Replicase-containing RNA vectors are significantly more immunogenic than conventional plasmids, immunizing mice at doses as low as 0.1 μg of nucleic acid injected once intramuscularly. Cells transfected with ‘self-replicating’ vectors briefly produce large amounts of antigen before undergoing apoptotic death. This death is a likely result of requisite double-stranded (ds) RNA intermediates, which also have been shown to super-activate DC. Thus, the enhanced immunogenicity of ‘self-replicating’ genetic vaccines may be a result of the production of pro-inflammatory dsRNA, which mimics an RNA-virus infection of host cells. PMID:10580187

Current Efforts and Future Prospects in the Development of Live Mycobacteria as Vaccines

PubMed Central

Porcelli, Steven A.; Ng, Tony W.; Saavedra-Avila, Noemi A; Kennedy, Steven C.; Carreno, Leandro J.

2016-01-01

Summary The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that are designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers. PMID:26366616

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

PubMed Central

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-01-01

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

Comparison of immune responses to different foot-and-mouth disease genetically engineered vaccines in guinea pigs.

PubMed

Yao, Qingxia; Qian, Ping; Huang, Qinfeng; Cao, Yi; Chen, Huanchun

2008-01-01

The P12A3C gene from FMDV (serotype O) encoding the capsid precursor protein, and the highly immunogenic gene FHG, which encodes multiple epitopes of FMDV capsid proteins, were inserted into eukaryotic expression vectors to compare different candidate genetically engineered vaccines for foot-and-mouth disease (FMD). A modified live pseudorabies virus (MLPRV) was also used to deliver P12A3C. Guinea pigs were inoculated intramuscularly with the candidate vaccines to compare the ability to elicit immunity of the DNA vector and a live viral vector. An indirect enzyme-linked immunosorbent assay (iELISA), virus-neutralization test and lymphoproliferation assay were used to detect antibody and cellular responses. The group immunized with P12A3C delivered by MLPRV produced significantly greater antibody and cellular responses indicating that MLPRV has a greater ability to mediate exogenous gene delivery than the plasmid DNA vector. Comparison of the immune responses induced by P12A3C and FHG, which were both mediated by DNA plasmids, showed that FHG and P12A3C elicited similar cellular responses, while P12A3C induced higher antibody levels, suggesting that P12A3C is a more powerful immunogen than FHG. In challenge experiments, guinea pigs vaccinated with P12A3C delivered by MLPRV were protected fully from FMDV challenge, whereas guinea pigs vaccinated with P12A3C or FHG delivered by DNA plasmid were only protected partially. This study provides a basis for future construction of a genetically engineered vaccine for FMDV.

Increase in Genetic Diversity of Haemophilus influenzae Serotype b (Hib) Strains after Introduction of Hib Vaccination in The Netherlands

PubMed Central

Schouls, Leo M.; van der Ende, Arie; van de Pol, Ingrid; Schot, Corrie; Spanjaard, Lodewijk; Vauterin, Paul; Wilderbeek, Dorus; Witteveen, Sandra

2005-01-01

Recently, there has been an increase in The Netherlands in the number of cases of invasive disease caused by Haemophilus influenzae serotype b (Hib). To study a possible change in the Hib population that could explain the rise in incidence, a multiple-locus variable number tandem repeats analysis (MLVA) was developed to genotype H. influenzae isolates. The MLVA enabled the differentiation of H. influenzae serotype b strains with higher discriminatory power than multilocus sequence typing (MLST). MLVA profiles of noncapsulated H. influenzae and H. influenzae serotype f strains were more heterogeneous than serotype b strains and were distinct from Hib, although some overlap occurred. The MLVA was used to genotype a collection of 520 H. influenzae serotype b strains isolated from patients in The Netherlands with invasive disease. The strains were collected from 1983 from 2002, covering a time period of 10 years before and 9 years after the introduction of the Hib vaccine in the Dutch national vaccination program. MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced. Hib strains isolated from patients older than 4 years in age were genetically diverse, and no significant change in diversity was seen after the introduction of the vaccine. These observations suggest that after the introduction of the Hib vaccine young children no longer constitute the reservoir for Hib and that they are infected by adults carrying genetically diverse Hib strains. PMID:15956392

Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine

PubMed Central

Haralambieva, Iana H.; Ovsyannikova, Inna G.; Umlauf, Benjamin J.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

2014-01-01

Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African

Current controversies in the USA regarding vaccine safety.

PubMed

Chatterjee, Archana; O'Keefe, Catherine

2010-05-01

As a result of the vaccines discovered in the 20th Century, parents and many healthcare providers of the 21st Century have limited or no experience with the devastating effects of diseases such as polio, smallpox or measles. Fear of disease has shifted to concerns regarding vaccine safety. Scientific evidence has refuted many of the misconceptions regarding vaccine safety; however, parental refusal of vaccines is increasing. Here we review six of the most prevalent controversies surrounding vaccine safety: the proposed causal relationship between receipt of the measles-mumps-rubella vaccine and autism; thimerosal as a potential trigger for autism; religious objection based on some vaccine viruses being grown in cell lines from aborted fetal tissues; parental worries that use of the human papillomavirus vaccine may lead to youth promiscuity; fears regarding the purported association between pertussis vaccination and adverse neurological outcomes; and concerns regarding too many vaccines overloading or weakening the infant immune system. Healthcare providers are ideally positioned to correct these misconceptions, but they must recognize and acknowledge parents' concerns, educate themselves on the latest scientific research that addresses these, and dedicate sufficient time to discuss vaccine safety with worried parents.

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

PubMed

Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity

PubMed Central

Julik, Emily; Reyes-del Valle, Jorge

2017-01-01

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine. PMID:28934110

Vaccination Against Dengue: Challenges and Current Developments.

PubMed

Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

2016-01-01

Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

Application of pharmacogenomics to vaccines

PubMed Central

Poland, Gregory A; Ovsyannikova, Inna G; Jacobson, Robert M

2009-01-01

The field of pharmacogenomics and pharmacogenetics provides a promising science base for vaccine research and development. A broad range of phenotype/genotype data combined with high-throughput genetic sequencing and bioinformatics are increasingly being integrated into this emerging field of vaccinomics. This paper discusses the hypothesis of the ‘immune response gene network’ and genetic (and bioinformatic) strategies to study associations between immune response gene polymorphisms and variations in humoral and cellular immune responses to prophylactic viral vaccines, such as measles–mumps–rubella, influenza, HIV, hepatitis B and smallpox. Immunogenetic studies reveal promising new vaccine targets by providing a better understanding of the mechanisms by which gene polymorphisms may influence innate and adaptive immune responses to vaccines, including vaccine failure and vaccine-associated adverse events. Additional benefits from vaccinomic studies include the development of personalized vaccines, the development of novel vaccines and the development of novel vaccine adjuvants. PMID:19450131

Current approaches to the development of vaccines effective against parainfluenza viruses

PubMed Central

Murphy, B. R.

1988-01-01

Infection of infants and children with parainfluenza viruses can lead to serious lower respiratory tract disease. In order to review new information on the genetic organization, epidemiology, and immunobiology of these viruses and of respiratory syncytial virus, WHO, in conjunction with the National Institute of Allergy and Infectious Diseases, held a workshop in Bethesda, MD, USA, 4-5 May 1987. New data on the immunobiology and epidemiology of human parainfluenza 3 virus were presented that should facilitate the development of a vaccine against this pathogen. PMID:2844427

Biological characteristics of genetic variants of Urabe AM9 mumps vaccine virus.

PubMed

Wright, K E; Dimock, K; Brown, E G

2000-03-01

The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguishable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuraminidase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation was detected in plaque purified viruses from the Urabe AM9 vaccine by examining the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells with plaque purified viruses with a G at nt 1081 of the HN gene produced large, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses were ts. In contrast, half of the plaque purified viruses with an A at nt 1081 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts viruses possessed a unique aa substitution at aa 468 of HN. The remaining A(1081) viruses were not ts, produced large plaques but little CPE, and grew to titres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associated with post-vaccination illness were similar to these non-ts A(1081) viruses, but could be further sub-divided into two groups on the basis of a difference at aa 464 of HN. The post-vaccination isolates may represent insufficiently attenuated components of the vaccine, while the G(1081) and ts subset of A(1081) viruses may be more fully attenuated.

[Preventive and therapeutic effect of genetic vaccine based on recombinant alpha virus against mouse mastocytoma P815].

PubMed

Ni, Bing; Yang, Ri-gao; Li, Yan-qiu; Wu, Yu-zhang

2004-01-01

To explore the immunological effect of genetic vaccine based on alpha-virus and to seek out better forms of gene vaccines. Expression plasmid P1A/pSMART2a and packaging plasmid helper were cotransfected into mammalian 293 cells by calcium phosphate precipitation method and high level of recombinant alpha-virus P1A/SFV was prepared. Following identification of rSFV and its expression, BALB/c mice were inoculated with rSFV, and the production of antigen-specific antibody and the cytotoxic effect of CTLs were determined. In the preventive and therapeutic experiments, the percents of tumor-free and of survival mice immunized with rSFV were observed. The recombinant SFV could express correctly in cultured cells. After being inoculated into the mice, rSFV could prime stronger CTL response than that in control mice. When the ratio of E/T cells was 100:1, the (51)Cr release rate reached 75%. No antibody could be detected in mice from all groups. The immunological effect of P1A/SFV among all groups was the best in both preventive and therapeutic experiment within experimental deadline. On 60th day in preventive experiment, the percent of tumor-free animal in P1A/SFV group reached 60%, whereas that was only 20% in P1A/pCI-neogroup. On 60th day in therapeutic experiment, survival rate of mice in P1A/SFV group reached 50%, but only 10% mice could survive in all control groups. Compared with common gene vaccines, the genetic vaccine based on recombinant SFV has the best immunological effect, which provides some new strategies for clinical genetic therapy of tumors.

Killed whole-HIV vaccine; employing a well established strategy for antiviral vaccines.

PubMed

Kang, C Yong; Gao, Yong

2017-09-12

The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1. This genetically modified virus (gmHIV-1 NL4-3 ) was propagated in a human T cell line followed by virus purification and inactivation by aldrithiol-2 and γ-irradiation. We found that SAV001 was well tolerated with no serious adverse events. HIV-1 NL4-3 -specific polymerase chain reaction showed no evidence of vaccine virus replication in participants receiving SAV001 and in human T cells infected in vitro. Furthermore, SAV001 with an adjuvant significantly increased the antibody response to HIV-1 structural proteins. Moreover, antibodies in the plasma from these vaccinations neutralized tier I and tier II of HIV-1 B, A, and D subtypes. These results indicated that the killed whole-HIV vaccine is safe and may trigger appropriate immune responses to prevent HIV infection. Utilization of this killed whole-HIV vaccine strategy may pave the way to develop an effective HIV vaccine.

Genetically Engineered, Live Attenuated Vaccines Protect Nonhuman Primates Against Aerosol Challenge with a Virulent IE Strain of Venezuelan Equine Encephalitis Virus

DTIC Science & Technology

2005-01-21

integrated moving average ( ARIMA ) model [15,19]. Fore- casted values for the postexposure time periods were based on the training model extrapolated...Smith JF. Genetically engineered, live attenuated vaccines or Venezuelan equine encephalitis: testing in animal models . Vaccine 2003;21(25–26):3854–62...encephalitis: testing in animal models . Vaccine 2003;21(25-26):3854-62] and IE strains of VEE viruses. 15. SUBJECT TERMS Venezuelan equine

Single-cycle adenovirus vectors in the current vaccine landscape.

PubMed

Barry, Michael

2018-02-01

Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

Development of a broadly protective modified-live virus vaccine candidate against porcine reproductive and respiratory syndrome virus

USDA-ARS?s Scientific Manuscript database

Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circul...

Genetic and antigenic relationship of foot-and-mouth disease virus serotype O isolates with the vaccine strain O1/BFS.

PubMed

Xu, Wanhong; Zhang, Zhidong; Nfon, Charles; Yang, Ming

2018-05-15

Foot-and-mouth disease serotype O viruses (FMDV/O) are responsible for the most outbreaks in FMD endemic countries. O1/BFS is one of the recommended FMD/O vaccine strains by World Reference Laboratory for FMD. In the current study, FMDV/O1 BFS vaccine strain and serotype O field isolates (45) were analyzed phylogenetically and antigenically to gain more insight into the genetic and antigenic characteristics of the vaccine strain and field isolates. O1/BFS showed similarity with 89% of the field isolates using a virus neutralization test (VNT). The P1 region encoding the FMDV capsid was sequenced and analysed for 46 strains of FMDV/O. Phylogenetic analysis showed these viruses originated from five continents and covered eight of 11 reported topotypes. Five isolates that demonstrated low antigenic similarities with O1/BFS were analyzed for their antigenic variation at the known neutralizing antigenic sites. Three of the five isolates demonstrated unique amino acid substitutions at various antigenic sites. No unique amino acid substitutions were observed for the other two unmatched isolates. Positively selected residues were identified on the surface of the FMD virus capsid supporting that it is important to continuously monitor field isolates for their antigenic and phenotypic changes. In conclusion, the vaccine strain O1/BFS is likely to confer protection against 89% of the 45 FMDV/O isolates based on VNT. Thus O1/BFS vaccine strain is still suitable for use in global FMD serotype O outbreak control. Combining data from phylogenetic, molecular and antigenic analysis can provide improvements in the process of vaccine selection. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Current Trends in West Nile Virus Vaccine Development

PubMed Central

Amanna, Ian J.; Slifka, Mark K.

2014-01-01

West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. PMID:24689659

DNA-launched live-attenuated vaccines for biodefense applications

PubMed Central

Pushko, Peter; Lukashevich, Igor S.; Weaver, Scott C.; Tretyakova, Irina

2016-01-01

Summary A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses. PMID:27055100

Sieve analysis in HIV-1 vaccine efficacy trials.

PubMed

Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

Multi-population Genomic Relationships for Estimating Current Genetic Variances Within and Genetic Correlations Between Populations.

PubMed

Wientjes, Yvonne C J; Bijma, Piter; Vandenplas, Jérémie; Calus, Mario P L

2017-10-01

Different methods are available to calculate multi-population genomic relationship matrices. Since those matrices differ in base population, it is anticipated that the method used to calculate genomic relationships affects the estimate of genetic variances, covariances, and correlations. The aim of this article is to define the multi-population genomic relationship matrix to estimate current genetic variances within and genetic correlations between populations. The genomic relationship matrix containing two populations consists of four blocks, one block for population 1, one block for population 2, and two blocks for relationships between the populations. It is known, based on literature, that by using current allele frequencies to calculate genomic relationships within a population, current genetic variances are estimated. In this article, we theoretically derived the properties of the genomic relationship matrix to estimate genetic correlations between populations and validated it using simulations. When the scaling factor of across-population genomic relationships is equal to the product of the square roots of the scaling factors for within-population genomic relationships, the genetic correlation is estimated unbiasedly even though estimated genetic variances do not necessarily refer to the current population. When this property is not met, the correlation based on estimated variances should be multiplied by a correction factor based on the scaling factors. In this study, we present a genomic relationship matrix which directly estimates current genetic variances as well as genetic correlations between populations. Copyright © 2017 by the Genetics Society of America.

Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

PubMed

Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

2015-02-01

Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

Biosafety evaluation of recombinant live oral bacterial vaccines in the context of European regulation.

PubMed

Favre, Didier; Viret, Jean-François

2006-05-01

Live bacterial vaccines represent a highly valid preventive strategy in the fight against infectious disease. However, the road from research to market is peppered with hurdles, one of which is the requirement for high biosafety characteristics, which the candidate vaccine has to display. In Europe, the European Agency for the evaluation of medicinal products (EMEA) is the relevant authority regulating the licensure of genetically engineered vaccines. For this purpose, the agency may rely on several directives and guidelines defined in the past 15 years. As for live vaccines containing genetically modified organisms (GMOs) susceptible to be released into the environment, Directive 2001/18/EC determines the framework and principles of an environmental risk assessment (ERA) process, the results of which constitute an important section of the vaccine registration package submitted to registration authorities. In this article, we address the implications of current European regulations for the approval of live oral bacterial vaccines with emphasis on the assessment of potential risks associated with environmental release. Biosafety aspects of already registered and some promising live bacterial vaccine strains will be briefly discussed.

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

PubMed Central

Nakayama, Yoshikazu; Aruga, Atsushi

2015-01-01

Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

PubMed

Volz, A; Sutter, G

2017-01-01

Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

Genetic diversity of transmission-blocking vaccine candidate Pvs48/45 in Plasmodium vivax populations in China.

PubMed

Feng, Hui; Gupta, Bhavna; Wang, Meilian; Zheng, Wenqi; Zheng, Li; Zhu, Xiaotong; Yang, Yimei; Fang, Qiang; Luo, Enjie; Fan, Qi; Tsuboi, Takafumi; Cao, Yaming; Cui, Liwang

2015-12-01

The male gamete fertilization factor P48/45 in malaria parasites is a prime transmission-blocking vaccine (TBV) candidate. Efforts to develop antimalarial vaccines are often thwarted by genetic diversity of the target antigens. Here we evaluated the genetic diversity of Pvs48/45 gene in global Plasmodium vivax populations. We determined 200 Pvs48/45 sequences collected from temperate and subtropical parasite populations in China. Population genetic and evolutionary analyses were performed to determine the levels of genetic diversity, potential signature of selection, and population differentiation. Analysis of the Pvs48/45 sequences from 200 P. vivax parasites collected in a temperate and a tropical region revealed a low level of genetic diversity (π = 0.0012) with 14 single nucleotide polymorphisms, of which 11 were nonsynonymous. Analysis of 344 Pvs48/45 sequences from nine worldwide P. vivax populations detected a total of 38 haplotypes, of which 13 haplotypes were present only once. Multiple tests for selection confirmed a signature of positive selection on Pvs48/45 with selection skewed to the second cysteine domain. Haplotype network analysis and Wright's fixation index showed large geographical differentiation with the presence of continent-or region-specific mutations in this gene. Pvs48/45 displays low levels of genetic diversity with the presence of region-specific mutations. Some of the mutations may be potential epitope targets based on their positions in the predicted structure, highlighting the need for future evaluation of these mutations in designing Pvs48/45-based TBV.

Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation.

PubMed

Barrett, Alan D T

2018-01-01

Zika virus (ZIKV), a mosquito-borne flavivirus, was first identified in the 1940s in Uganda in Africa and emerged in the Americas in Brazil in May 2015. In the 30 months since ZIKV emerged as a major public health problem, spectacular progress has been made with vaccine development cumulating with the publication of three reports of phase 1 clinical trials in the 4th quarter of 2017. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralizing antibodies, although these varied by vaccine candidate and dosing regimen. These results suggest that a Zika vaccine can be developed and that phase 2 clinical trials are warranted. However, it is difficult to compare the results from the different phase 1 studies or with neutralizing antibodies induced by licensed flavivirus vaccines (Japanese encephalitis, tick-borne encephalitis, and yellow fever) as neutralizing antibody assays vary and, unfortunately, there are no standards for Zika virus neutralizing antibodies. In addition to clinical studies, substantial progress continues to be made in nonclinical development, particularly in terms of the ability of candidate vaccines to protect reproductive tissues, and the potential use of monoclonal antibodies for passive prophylaxis.

Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

PubMed

Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

2015-09-01

For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised. © 2014 EVJ Ltd.

Next-generation dengue vaccines: novel strategies currently under development.

PubMed

Durbin, Anna P; Whitehead, Stephen S

2011-10-01

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

Overview of recent DNA vaccine development for fish

USGS Publications Warehouse

Kurath, G.; ,

2005-01-01

Since the first description of DNA vaccines for fish in 1996, numerous studies of genetic immunisation against the rhabdovirus pathogens infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV) have established their potential as both highly efficacious biologicals and useful basic research tools. Single small doses of rhabdovirus DNA constructs provide extremely strong protection against severe viral challenge under a variety of conditions. DNA vaccines for several other important fish viruses, bacteria, and parasites are under investigation, but they have not yet shown high efficacy. Therefore, current research is focussed on mechanistic studies to understand the basis of protection, and on improvement of the nucleic acid vaccine applications against a wider range of fish pathogens.

African swine fever virus: current state and future perspectives in vaccine and antiviral research.

PubMed

Zakaryan, Hovakim; Revilla, Yolanda

2016-03-15

African swine fever (ASF) is among the most significant of swine diseases for which no effective vaccines and antivirals are available. The disease, which is endemic in Africa, was introduced to Trans-Caucasian countries and the Russian Federation in 2007, where it remains prevalent today among domestic pigs and wild boars. Although some measures were implemented, ASF continues to pose a global risk for all countries, and thereby highlighting the importance of vaccine and antiviral research. In this review, an overview of research efforts toward the development of effective vaccines during the past decades is presented. As an alternative to vaccine development, the current state in antiviral research against ASFV is also presented. Finally, future perspectives in vaccine and antiviral research giving emphasis on some strategies that may allow researchers to develop effective countermeasures against ASF are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Sieve analysis in HIV-1 vaccine efficacy trials

PubMed Central

Edlefsen, Paul T.; Gilbert, Peter B.; Rolland, Morgane

2013-01-01

Purpose of review The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. Recent findings The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 and RV144, led to numerous studies in the last five years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Summary Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons while correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection. PMID:23719202

[Chickenpox and shingles: one virus, two diseases and current vaccination recommendations in Switzerland].

PubMed

Eckert, Nadine; Masserey Spicher, Virginie

2016-01-01

Adults, pregnant women, premature babies and immunocompromised persons are at increased risk for varicella complications. Therefore the current Swiss vaccination recommendations against varicella include a general recommendation for 11 to 15 year old adolescents with a negative varicella history, as well as a specific recommendation for risk groups. The goal of both recommendations is to reduce varicella complications in persons most at risk. The vaccine is not universally recommended for all toddlers in Switzerland, while this is the case in some countries such as the United States. Pros and cons of different vaccination strategies, as well as possible short- and long-term effects on herpes zoster incidence are taken into account. In the United States, there was a marked decline in incidence and hospitalisations, but an increased herpes zoster incidence in the short term. Finally, public health aspects of herpes zoster, post-herpetic neuralgia and possible vaccination strategies are outlined.

Excretion of Wild-Type and Vaccine-Derived Poliovirus in the Feces of Poliovirus Receptor-Transgenic Mice

PubMed Central

Boot, Hein J.; Kasteel, Daniella T. J.; Buisman, Anne-Marie; Kimman, Tjeerd G.

2003-01-01

The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains. PMID:12743311

US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

PubMed Central

Unger, Elizabeth R.; Thompson, Trevor D.; Lynch, Charles F.; Hernandez, Brenda Y.; Lyu, Christopher W.; Steinau, Martin; Watson, Meg; Wilkinson, Edward J.; Hopenhayn, Claudia; Copeland, Glenn; Cozen, Wendy; Peters, Edward S.; Huang, Youjie; Saber, Maria Sibug; Altekruse, Sean; Goodman, Marc T.

2015-01-01

Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)–associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. Conclusions: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. PMID:25925419

Intradermal delivery of vaccines: potential benefits and current challenges

PubMed Central

Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

2011-01-01

Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

Current Status of Rift Valley Fever Vaccine Development

PubMed Central

Faburay, Bonto; LaBeaud, Angelle Desiree; McVey, D. Scott; Wilson, William C.; Richt, Juergen A.

2017-01-01

Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease. PMID:28925970

Advances in hepatitis immunization (A, B, E): public health policy and novel vaccine delivery.

PubMed

Hendrickx, Greet; Vorsters, Alex; Van Damme, Pierre

2012-10-01

This review offers an update on hepatitis A, B and E vaccines based on relevant literature published in 2011-2012. Hepatitis A and B vaccines have been commercially available for years; however, the development of the hepatitis E vaccine is still facing some challenges. Current scientific evidence shows that both hepatitis A and B vaccines confer long-term protection. These data supported the updated recommendations from the WHO on hepatitis A and B vaccines and the respective booster policy. In addition, a single-dose hepatitis A vaccination programme may be an option for some intermediate endemic countries, as far as the epidemiological situation is further monitored. Recent data illustrate the co-administration of hepatitis A with infant vaccines, as well as the interchangeability with other hepatitis A vaccines. Two genetically engineered hepatitis E vaccines are currently in development, showing more than 95% protective efficacy. Follow-up of vaccinated individuals confirms the long-term protection offered by the hepatitis A as well as hepatitis B vaccines. Data confirm the safety and immunogenicity profile of both vaccines, also when used in patient groups. The first data on the hepatitis E vaccine look promising, but questions on cross-protection, long-term efficacy and safety and immunogenicity in pregnant women and children less than 2 years remain unanswered.

Rift Valley fever vaccines: current and future needs.

PubMed

Dungu, Baptiste; Lubisi, Baratang A; Ikegami, Tetsuro

2018-04-01

Rift Valley fever (RVF) is a zoonotic mosquito-borne bunyaviral disease associated with high abortion rates, neonatal deaths, and fetal malformations in ruminants, and mild to severe disease in humans. Outbreaks of RVF cause huge economic losses and public health impacts in endemic countries in Africa and the Arabian Peninsula. A proper vaccination strategy is important for preventing or minimizing outbreaks. Vaccination against RVF is not practiced in many countries, however, due to absence or irregular occurrences of outbreaks, despite serological evidence of RVF viral activity. Nonetheless, effective vaccination strategies, and functional national and international multi-disciplinary networks, remain crucial for ensuring availability of vaccines and supporting execution of vaccination in high risk areas for efficient response to RVF alerts and outbreaks. Copyright © 2018 Elsevier B.V. All rights reserved.

Vaccines and vaccination strategies against human cutaneous leishmaniasis.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2009-05-01

One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae.

PubMed

Douce, Gill; Ross, Kirsty; Cowan, Graeme; Ma, Jiangtao; Mitchell, Tim J

2010-04-19

Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens. Copyright 2010 Elsevier Ltd. All rights reserved.

New genetic associations detected in a host response study to hepatitis B vaccine.

PubMed

Davila, S; Froeling, F E M; Tan, A; Bonnard, C; Boland, G J; Snippe, H; Hibberd, M L; Seielstad, M

2010-04-01

The immune response to hepatitis B vaccination differs greatly among individuals, with 5-10% of healthy people failing to produce protective levels of antibodies. Several factors have been implicated in determining this response, chiefly individual genetic variation and age. Aiming to identify genes involved in the response to hepatitis B vaccination, a two-stage investigation of 6091 single-nucleotide polymorphisms (SNPs) in 914 immune genes was performed in an Indonesian cohort of 981 individuals showing normal levels of anti-HBs versus 665 individuals displaying undetectable levels of anti-HBs 18 months after initial dose of the vaccine. Of 275 SNPs identified in the first stage (476 normal/372 nonresponders) with P<0.05, significant associations were replicated for 25 polymorphisms in 15 genes (503 normal/295 nonresponders). We validated previous findings (HLA-DRA, rs5000563, P-value combined=5.57 x 10(-10); OR (95%CI)=0.61 (0.52-0.71)). In addition, we detected a new association outside of the human leukocyte antigen loci region that passed correction for multiple testing. This SNP is in the 3' downstream region of FOXP1, a transcription factor involved in B-cell development (P-value combined=9.2 x 10(-6); OR (95%CI)=1.38 (1.2-1.6)).These findings might help to understand the biological reasons behind vaccine failure and other aspects of variation in the immune responses of healthy individuals.

Genetic variation in potential Giardia vaccine candidates cyst wall protein 2 and α1-giardin.

PubMed

Radunovic, Matej; Klotz, Christian; Saghaug, Christina Skår; Brattbakk, Hans-Richard; Aebischer, Toni; Langeland, Nina; Hanevik, Kurt

2017-08-01

Giardia is a prevalent intestinal parasitic infection. The trophozoite structural protein a1-giardin (a1-g) and the cyst protein cyst wall protein 2 (CWP2) have shown promise as Giardia vaccine antigen candidates in murine models. The present study assesses the genetic diversity of a1-g and CWP2 between and within assemblages A and B in human clinical isolates. a1-g and CWP2 sequences were acquired from 15 Norwegian isolates by PCR amplification and 20 sequences from German cultured isolates by whole genome sequencing. Sequences were aligned to reference genomes from assemblage A2 and B to identify genetic variance. Genetic diversity was found between assemblage A and B reference sequences for both a1-g (90.8% nucleotide identity) and CWP2 (82.5% nucleotide identity). However, for a1-g, this translated into only 3 amino acid (aa) substitutions, while for CWP2 there were 41 aa substitutions, and also one aa deletion. Genetic diversity within assemblage B was larger; nucleotide identity 92.0% for a1-g and 94.3% for CWP2, than within assemblage A (nucleotide identity 99.0% for a1-g and 99.7% for CWP2). For CWP2, the diversity on both nucleotide and protein level was higher in the C-terminal end. Predicted antigenic epitopes were not affected for a1-g, but partially for CWP2. Despite genetic diversity in a1-g, we found aa sequence, characteristics, and antigenicity to be well preserved. CWP2 showed more aa variance and potential antigenic differences. Several CWP2 antigens might be necessary in a future Giardia vaccine to provide cross protection against both Giardia assemblages infecting humans.

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses

PubMed Central

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nuntawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-01-01

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate (A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby Canine Kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 29 HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. PMID:22230579

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses.

PubMed

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nantawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-02-14

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby canine kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 2(9) HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Current state and challenges in developing oral vaccines.

PubMed

Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A

2017-05-15

While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.

Current and future vaccines and vaccination strategies against infectious laryngotracheitis (ILT) respiratory disease of poultry.

PubMed

García, Maricarmen

2017-07-01

Infectious laryngotracheitis (ILT) is an economically important respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease. Two types of vaccines, live attenuated and recombinant viral vector, are commercially available. The first generation of GaHV-1 vaccines available since the early 1960's are live viruses, attenuated by continuous passages in cell culture or embryos. These vaccines significantly reduce mortalities and, in particular, the chicken embryo origin (CEO) vaccines have shown to limit outbreaks of the disease. However, the CEO vaccines can regain virulence and become the source of outbreaks. Recombinant viral vector vaccines, the second generation of GaHV-1 vaccines, were first introduced in the early 2000's. These are Fowl Pox virus (FPV) and Herpes virus of turkeys (HVT) vectors expressing one or multiple GaHV-1 immunogenic proteins. Recombinant viral vector vaccines are considered a much safer alternative because they do not regain virulence. In the face of challenge, they improve bird performance and ameliorate clinical signs of the disease but fail to reduce shedding of the challenge virus increasing the likelihood of outbreaks. At the moment, several new strategies are being evaluated to improve both live attenuated and viral vector vaccines. Potential new live vaccines attenuated by deletion of genes associated with virulence or by selection of CEO viral subpopulations that do not exhibit increased virulence upon passages in birds are being evaluated. Also new vector alternatives to express GaHV-1 glycoproteins in Newcastle diseases virus (NDV) or in modified very virulent (vv) serotype I Marek's disease virus (MDV) were developed and evaluated. Copyright © 2016 Elsevier B.V. All rights reserved.

Yellow fever vaccine-associated viscerotropic disease: current perspectives.

PubMed

Thomas, Roger E

2016-01-01

To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles. All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers. All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People's Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died). Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity.

Yellow fever vaccine-associated viscerotropic disease: current perspectives

PubMed Central

Thomas, Roger E

2016-01-01

Purpose To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Literature search Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles. Methods All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers. Results All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People’s Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died). Conclusion Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity. PMID:27784992

Fish Vaccines: Current State and Future Trends

USDA-ARS?s Scientific Manuscript database

A vaccine is a preventive tool used in a health management strategy for the control of infectious diseases. For more than 100 years, vaccines have proved to be effective for preventing infectious disease outbreaks in humans, poultry and other food animals. In aquaculture, the development and use of...

Evaluation of fusion protein cleavage site sequences of Newcastle disease virus in genotype matched vaccines.

PubMed

Kim, Shin-Hee; Chen, Zongyan; Yoshida, Asuka; Paldurai, Anandan; Xiao, Sa; Samal, Siba K

2017-01-01

Newcastle disease virus (NDV) causes a devastating poultry disease worldwide. Frequent outbreaks of NDV in chickens vaccinated with conventional live vaccines suggest a need to develop new vaccines that are genetically matched against circulating NDV strains, such as the genotype V virulent strains currently circulating in Mexico and Central America. In this study, a reverse genetics system was developed for the virulent NDV strain Mexico/01/10 strain and used to generate highly attenuated vaccine candidates by individually modifying the cleavage site sequence of fusion (F) protein. The cleavage site sequence of parental virus was individually changed to those of the avirulent NDV strain LaSota and other serotypes of avian paramyxoviruses (APMV serotype-2, -3, -4, -6, -7, -8, and -9). In general, these mutations affected cell-to-cell fusion activity in vitro and the efficiency of the F protein cleavage and made recombinant Mexico/01/10 (rMex) virus highly attenuated in chickens. When chickens were immunized with the rMex mutant viruses and challenged with the virulent parent virus, there was reduced challenge virus shedding compared to birds immunized with the heterologous vaccine strain LaSota. Among the vaccine candidates, rMex containing the cleavage site sequence of APMV-2 induced the highest neutralizing antibody titer and completely protected chickens from challenge virus shedding. These results show the role of the F protein cleavage site sequence of each APMV type in generating genotype V-matched vaccines and the efficacy of matched vaccine strains to provide better protection against NDV strains currently circulating in Mexico.

Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

PubMed

de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

2015-01-01

To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination.

PubMed

Horn, Johannes; Karch, André; Damm, Oliver; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hengel, Hartmut; Greiner, Wolfgang; Mikolajczyk, Rafael T

2016-07-02

Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

PubMed Central

2017-01-01

Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

PubMed Central

Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng

2013-01-01

Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840

Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection.

PubMed

Sack, Brandon; Kappe, Stefan H I; Sather, D Noah

2017-05-01

An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.

A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis.

PubMed

Xue, Jianmin; Chen, Xia; Selby, Dale; Hung, Chiung-Yu; Yu, Jieh-Juen; Cole, Garry T

2009-08-01

Coccidioidomycosis (also known as San Joaquin Valley fever) is an occupational disease. Workers exposed to outdoor dust which contains spores of the soil-inhabiting fungus have a significantly increased risk of respiratory infection. In addition, people with compromised T-cell immunity, the elderly, and certain racial groups, particularly African-Americans and Filipinos, who live in regions of endemicity in the southwestern United States have an elevated incidence of symptomatic infection caused by inhalation of spores of Coccidioides posadasii or Coccidioides immitis. Recurring epidemics and escalation of medical costs have helped to motivate production of a vaccine against valley fever. The major focus has been the development of a defined, T-cell-reactive, recombinant protein vaccine. However, none of the products described to date have provided full protection to coccidioidal disease-susceptible BALB/c mice. Here we describe the first genetically engineered, live, attenuated vaccine that protects both BALB/c and C57BL/6 mice against coccidioidomycosis. Two chitinase genes (CTS2 and CTS3) were disrupted to yield the attenuated strain, which was unable to endosporulate and was no longer infectious. Vaccinated survivors mounted an immune response characterized by production of both T-helper-1- and T-helper-2-type cytokines. Histology revealed well-formed granulomas and markedly diminished inflammation. Significantly fewer organisms were observed in the lungs of survivors than in those of nonvaccinated mice. Additional investigations are required to further define the nature of the live, attenuated vaccine-induced immunity against Coccidioides infection.

US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines.

PubMed

Saraiya, Mona; Unger, Elizabeth R; Thompson, Trevor D; Lynch, Charles F; Hernandez, Brenda Y; Lyu, Christopher W; Steinau, Martin; Watson, Meg; Wilkinson, Edward J; Hopenhayn, Claudia; Copeland, Glenn; Cozen, Wendy; Peters, Edward S; Huang, Youjie; Saber, Maria Sibug; Altekruse, Sean; Goodman, Marc T

2015-06-01

This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Vaccination against mosquito borne viral infections: current status.

PubMed

Wiwanitkit, Viroj

2007-12-01

Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japanese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.

Malaria vaccines: the case for a whole-organism approach.

PubMed

Pinzon-Charry, Alberto; Good, Michael F

2008-04-01

Malaria is a significant health problem causing morbidity and mortality worldwide. Vaccine development has been an imperative for decades. However, the intricacy of the parasite's lifecycle coupled with the lack of evidence for robust infection-induced immunity has made vaccine development exceptionally difficult. To review some of the key advances in the field and discuss potential ways forward for a whole-organism vaccine. The authors searched PubMed using the words 'malaria and vaccine'. We searched for manuscripts detailing antigen characterisation and vaccine strategies with emphasis on subunit versus whole-parasite approaches. Abstracts were selected and relevant articles are discussed. The searches were not restricted by language or date. The early cloning of malaria antigens has fuelled rapid development of subunit vaccines. However, the disappointing results of clinical trials have resulted in reappraisal of current strategies. Whole-parasite approaches have re-emerged as an alternative strategy. Immunization using radiation or genetically attenuated sporozoites has been shown to result in sterile immunity and immunization with blood-stage parasites curtailed by antimalarials has demonstrated delayed parasitemia in rodent models as well as in human malaria.

Novel immunotherapy vaccine development.

PubMed

Jutel, Marek; Akdis, Cezmi A

2014-12-01

Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

Hepatitis B vaccination of premature infants: a reassessment of current recommendations for delayed immunization.

PubMed

Losonsky, G A; Wasserman, S S; Stephens, I; Mahoney, F; Armstrong, P; Gumpper, K; Dulkerian, S; West, D J; Gewolb, I H

1999-02-01

Current American Academy of Pediatrics and United States Public Health Service Immunization Practices Advisory Committee recommendations for hepatitis B immunization in premature infants weighing <2 kg at birth born to hepatitis B surface antigen (HBSAg)-negative mothers are to delay the initiation of vaccination until such infants reach 2 kg or until 2 months of age. This proposal to delay vaccination at birth in these low-risk infants was based on limited studies not conducted in the United States. We sought to reassess current recommendations to delay administration of hepatitis B vaccine in low-risk premature infants by determining the immunogenicity of early hepatitis B vaccination in a US population and identifying variables associated with poor immunogenicity. A total of 148 infants <37 weeks' gestation born to mothers negative for HBSAg were recruited at birth and stratified to three birth weight groups: <1000 g, 1000 to 1500 g, and >1500 g. Recombinant hepatitis B vaccine was administered within the first week of life, at 1 to 2 months of age, and at 6 to 7 months of age. Serum obtained at birth and after the second and third doses of vaccine was tested for antibody to HBSAg. Variables associated with poor response were sought prospectively by collecting demographic and clinical data. A total of 118 subjects (83%) completed the study. Postsecond dose sera were available for 117 infants and postthird dose sera were available for 112 infants. The seroprotection rate (attaining >/=10 mIU/mL HBS antibody) after two doses was low (25%) regardless of birth weight; infants weighing <1000 g at birth had the poorest response (11%). The seroprotection response rate after three doses of vaccine increased with birth weight; infants weighing 1500 g at birth (group 3; 84% response rate). The seroprotection response rate of group 3 infants after three

A genetically inactivated two-component acellular pertussis vaccine, alone or combined with tetanus and reduced-dose diphtheria vaccines, in adolescents: a phase 2/3, randomised controlled non-inferiority trial.

PubMed

Sricharoenchai, Sirintip; Sirivichayakul, Chukiat; Chokephaibulkit, Kulkanya; Pitisuttithum, Punnee; Dhitavat, Jittima; Pitisuthitham, Arom; Phongsamart, Wanatpreeya; Boonnak, Kobporn; Lapphra, Keswadee; Sabmee, Yupa; Wittawatmongkol, Orasri; Chinwangso, Pailinrut; Poredi, Indrajeet Kumar; Petre, Jean; Thai, Pham Hong; Viviani, Simonetta

2018-01-01

Increasing evidence shows that protection induced by acellular pertussis vaccines is short-lived, requiring repeated booster vaccination to control pertussis disease. We aimed to assess the safety and immunogenicity of a recombinant acellular pertussis vaccine containing genetically inactivated pertussis toxin and filamentous haemagglutinin, as either a monovalent vaccine (aP [PTgen/FHA] ) or in combination with tetanus and reduced-dose diphtheria vaccines (TdaP [PTgen/FHA] ), versus a licensed tetanus and reduced-dose diphtheria and acellular pertussis combination vaccine (Tdap). We did this phase 2/3, randomised controlled non-inferiority trial at two sites in Bangkok, Thailand. Healthy adolescents (aged 12-17 years) were randomly assigned (1:1:1), via a computer-generated randomisation list with block sizes of three, to receive one dose (0·5 mL) of aP (PTgen/FHA) , TdaP (PTgen/FHA) , or Tdap (comparator). Clinical research staff responsible for participant randomisation, vaccine preparation and administration, and accountability were aware of group allocation. However, allocation was concealed from all other site study staff, data management personnel, statisticians, laboratory staff, and study participants. The primary outcome was non-inferior immunogenicity of TdaP (PTgen/FHA) to Tdap based on seroconversion rates (a four-fold increase or more) for pertussis toxin and filamentous haemagglutinin IgG antibodies 28 days after vaccination, with a predefined 10% margin of equivalence. We did analysis by per protocol. This study is registered with the Thai Clinical Trial Registry, number TCTR20150703002. Between July 6 and Aug 20, 2015, we allocated 450 participants to receive one dose of TdaP (PTgen/FHA) (n=150), aP (PTgen/FHA) (n=150), or comparator Tdap (n=150). 28 days after vaccination, seroconversion rates for anti-pertussis toxin IgG were 96·6% (95% CI 93·8-99·5; n=144) in the TdaP (PTgen/FHA) group and 55·0% (47·1-63·0; n=82) in the comparator Tdap

Clinical experience with respiratory syncytial virus vaccines.

PubMed

Piedra, Pedro A

2003-02-01

Respiratory syncytial virus (RSV) infection is at times associated with life-threatening lower respiratory tract illness in infancy. Severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. Severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. However, RSV causes respiratory infections in all age groups. Indeed it is now recognized that RSV disease is responsible for significant morbidity and mortality in the geriatric population. RSV infection remains difficult to treat, and prevention is a worldwide goal. For this reason there has been an intensive effort to develop an effective and safe RSV vaccine. Initial infection with RSV affords limited protection to reinfection, yet repeated episodes decrease the risk for lower respiratory tract illness. In the 20 years from 1960 to 1980, trials of several candidate RSV vaccines failed to attain the desired safety and protection against natural infection. Some vaccine types either failed to elicit immunogenicity, as with the live subcutaneous vaccine, or resulted in exaggerated disease on natural exposure to the virus, as with the formalin-inactivated (FI) type. Currently vaccine candidates are being developed based on the molecular virology of RSV. Recent formulations of candidate RSV vaccines have focused on subunit vaccines [such as purified fusion protein (PFP)], subunit vaccines combined with nonspecific immune activating adjuvants, live attenuated vaccines (including cold passaged, temperature-sensitive or cpts mutants), genetically engineered live attenuated vaccines and polypeptide vaccines.

Hepatitis Vaccines

PubMed Central

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

Vaccines against Botulism.

PubMed

Sundeen, Grace; Barbieri, Joseph T

2017-09-02

Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin.

Vaccines against Botulism

PubMed Central

Sundeen, Grace; Barbieri, Joseph T.

2017-01-01

Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin. PMID:28869493

Rescue of a vaccine strain of peste des petits ruminants virus: In vivo evaluation and comparison with standard vaccine

PubMed Central

Muniraju, Murali; Mahapatra, Mana; Buczkowski, Hubert; Batten, Carrie; Banyard, Ashley C.; Parida, Satya

2015-01-01

Across the developing world peste des petits ruminants virus places a huge disease burden on agriculture, primarily affecting the production of small ruminant. The disease is most effectively controlled by vaccinating sheep and goats with live attenuated vaccines that provide lifelong immunity. However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In this study, we have established an efficient reverse genetics system for PPRV Nigeria 75/1 vaccine strain and, further rescued a version of PPRV Nigeria 75/1 vaccine strain that expresses eGFP as a novel transcription cassette and a version of PPRV Nigeria 75/1 vaccine strain with mutations in the haemagglutinin (H) gene to enable DIVA through disruption of binding to H by the C77 monoclonal antibody used in the competitive (c) H-ELISA. All three rescued viruses showed similar growth characteristics in vitro in comparison to parent vaccine strain and, following in vivo assessment the H mutant provided full protection in goats. Although the C77 monoclonal antibody used in the cH-ELISA was unable to bind to the mutated form of H in vitro, the mutation was not sufficient to enable DIVA in vivo. PMID:25444790

Historical habitat connectivity affects current genetic structure in a grassland species.

PubMed

Münzbergová, Z; Cousins, S A O; Herben, T; Plačková, I; Mildén, M; Ehrlén, J

2013-01-01

Many recent studies have explored the effects of present and past landscape structure on species distribution and diversity. However, we know little about the effects of past landscape structure on distribution of genetic diversity within and between populations of a single species. Here we describe the relationship between present and past landscape structure (landscape connectivity and habitat size estimated from historical maps) and current genetic structure in a perennial herb, Succisa pratensis. We used allozymes as co-dominant markers to estimate genetic diversity and deviation from Hardy-Weinberg equilibrium in 31 populations distributed within a 5 km(2) agricultural landscape. The results showed that current genetic diversity of populations was related to habitat suitability, habitat age, habitat size and habitat connectivity in the past. The effects of habitat age and past connectivity on genetic diversity were in most cases also significant after taking the current landscape structure into account. Moreover, current genetic similarity between populations was affected by past connectivity after accounting for current landscape structure. In both cases, the oldest time layer (1850) was the most informative. Most populations showed heterozygote excess, indicating disequilibrium due to recent gene flow or selection against homozygotes. These results suggest that habitat age and past connectivity are important determinants of distribution of genetic diversity between populations at a scale of a few kilometres. Landscape history may significantly contribute to our understanding of distribution of current genetic structure within species and the genetic structure may be used to better understand landscape history, even at a small scale. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

[Immune response to live influenza vaccine].

PubMed

Naĭkhin, A N; Rekstin, A R; Barantseva, I B; Donina, S A; Desheva, Iu A; Grigor'eva, E P; Kiseleva, I V; Rudenko, L G

2002-01-01

Priority data on the induction, by using a Russian live cold-adapted reassortant influenza vaccine (LIV), of the cellular and humoral immunity with regard for attenuation and genetic reassortment of vaccine stains as well as with regard for the age of vaccinated persons and the production of Th1 (IFNY, IL-2) and Th2 (IL-4) cytokine markers in vitro are presented. It was demonstrated in vivo that a pathogenic virus of the A group by far more actively induced the lymphocyte apoptosis as compared with attenuated genetically reassorted stains. Unlike the influenza pathogenic virus, the genetically attenuated and reassorted strain did not produce any negative effects on the induction of cellular immunity. A comparative study of the LIV immunogenic properties in vaccinated persons showed an advantage of LIV over inactivated influenza vaccine (IIV) in stimulating the cellular and local immunity in the elderly. Unlike IIV, LIV induced an active and balanced immune response developing due to Th1 and Th2 activation. LIV was found to stimulate well enough the production of IFN and IL-2 in both young and old persons.

Variability in Humoral Immunity to Measles Vaccine: New Developments

PubMed Central

Haralambieva, Iana H.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Whitaker, Jennifer A.; Poland, Gregory A.

2015-01-01

Despite the existence of an effective measles vaccine, resurgence in measles cases in the United States and across Europe has occurred, including in individuals vaccinated with two doses of the vaccine. Host genetic factors result in inter-individual variation in measles vaccine-induced antibodies, and play a role in vaccine failure. Studies have identified HLA and non-HLA genetic influences that individually or jointly contribute to the observed variability in the humoral response to vaccination among healthy individuals. In this exciting era, new high-dimensional approaches and techniques including vaccinomics, systems biology, GWAS, epitope prediction and sophisticated bioinformatics/statistical algorithms, provide powerful tools to investigate immune response mechanisms to the measles vaccine. These might predict, on an individual basis, outcomes of acquired immunity post measles vaccination. PMID:26602762

Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

PubMed

Yamamoto, D S; Nagumo, H; Yoshida, S

2010-06-01

'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Vaccines: the fourth century.

PubMed

Plotkin, Stanley A

2009-12-01

Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines.

Ebola virus vaccines: an overview of current approaches

PubMed Central

Marzi, Andrea; Feldmann, Heinz

2016-01-01

Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

PubMed

Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

2015-08-26

The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Worldwide genetic variability of the Duffy binding protein: insights into Plasmodium vivax vaccine development.

PubMed

Nóbrega de Sousa, Taís; Carvalho, Luzia Helena; Alves de Brito, Cristiana Ferreira

2011-01-01

The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP) makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBP(II)), known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBP(II) sequences will allow us to determine the minimum number of haplotypes (MNH) to be included in a DBP-based vaccine of broad coverage. For that, all DBP(II) sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBP(II) genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total) would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBP(II) sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48-84%). In addition, to identify related subgroups of DBP(II) sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBP(II) sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBP(II) variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations.

Elucidation of the full genetic information of Japanese rubella vaccines and the genetic changes associated with in vitro and in vivo vaccine virus phenotypes.

PubMed

Otsuki, Noriyuki; Abo, Hitoshi; Kubota, Toru; Mori, Yoshio; Umino, Yukiko; Okamoto, Kiyoko; Takeda, Makoto; Komase, Katsuhiro

2011-02-24

Rubella is a mild disease characterized by low-grade fever, and a morbilliform rash, but causes congenital defects in neonates born from mothers who suffered from rubella during the pregnancy. After many passages of wild-type rubella virus strains in various types of cultured cells, five live attenuated rubella vaccines were developed in Japan. An inability to elicit anti-rubella virus antibodies in experimentally infected animals was used as an in vivo marker phenotype of Japanese rubella vaccines. All Japanese rubella vaccine viruses exhibit a temperature-sensitive (ts) phenotype, and replicate very poorly at a high temperature. We determined the entire genome sequences of three Japanese rubella vaccines (Matsuba, TCRB19, and Matsuura), thereby completing the sequencing of all five Japanese rubella vaccines. In addition, the entire genome sequences of three vaccine progenitors were determined. Comparative nucleotide sequence analyses revealed mutations that were introduced into the genomes of the TO-336 and Matsuura vaccines during their production by laboratory passaging. Analyses involving cellular expression of viral P150 nonstructural protein-derived peptides revealed that the N1159S mutation conferred the ts phenotype on the TO-336 vaccine, and that reduced thermal stability of the P150 protease domain was a cause of the ts phenotype of some rubella vaccine viruses. The ts phenotype of vaccine viruses was not necessarily correlated with their inability to elicit humoral immune responses in animals. Therefore, the molecular mechanisms underlying the inability of these vaccines to elicit humoral responses in animals are more complicated than the previously considered mechanism involving the ts phenotype as the major cause. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.

PubMed

Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

2014-01-01

Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

Development of a novel oral vaccine against Mycobacterium avium paratuberculosis and Johne disease

PubMed Central

Johnston, C; Coffey, A; Sleator, RD

2010-01-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne disease, a granulomatous enteritis of cattle and other domesticated and wild ruminant species. Johne disease is prevalent worldwide and has a significant impact on the global agricultural economy. Current vaccines against Johne are insufficient in stemming its spread, and associated side-effects prevent their widespread use in control programs. Effective and safe vaccine strategies are needed. The main purpose of this paper is to propose and evaluate the development of a novel oral subunit-vaccine using a patho-biotechnological approach. This novel strategy, which harnesses patho-genetic elements from the intracellular pathogen Listeria monocytogenes, may provide a realistic route towards developing an effective next generation subunit vaccine against Johne disease and paratuberculosis. PMID:21326921

[Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

PubMed

Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

2010-12-01

Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Virus like particle-based vaccines against emerging infectious disease viruses.

PubMed

Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2016-08-01

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Human papillomavirus vaccines and vaccine implementation.

PubMed

de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

2008-11-01

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

PubMed

Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E

2015-01-01

No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

Peptide nanofiber hydrogel adjuvanted live virus vaccine enhances cross-protective immunity to porcine reproductive and respiratory syndrome virus

PubMed Central

Li, Xiangdong; Galliher-Beckley, Amy; Huang, Hongzhou; Sun, Xiuzhi; Shi, Jishu

2013-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in swine farms worldwide and is a major source of economic loss and animal suffering. Rapid genetic variation of PRRSV makes it difficult for current vaccines to confer protection against newly emerging strains. We recently demonstrated that a novel peptide nanofiber hydrogel (H9e) could act as a potent adjuvant for killed H1N1 vaccines. Therefore, the objective of this study was to evaluate H9e as an adjuvant for PRRSV modified live virus (MLV) vaccines. Pigs were vaccinated with Ingelvac PRRSV MLV with or without H9e adjuvant before being challenged with the VR-2332 (parental vaccine strain) or MN184A (genetically diverse strain) PRRSV. Pigs vaccinated with MLV+H9e had higher levels of circulating vaccine virus. More importantly, pigs vaccinated with MLV+H9e had improved protection against challenge by both PRRSV strains, as demonstrated by reduced challenge-induced viremia compared with pigs vaccinated with MLV alone. Pigs vaccinated with MLV+H9e had lower frequency of T-regulatory cells and IL-10 production but higher frequency of Th/memory cells and IFN-γ secretion than that in pigs vaccinated with MLV alone. Taken together, our studies suggest that the peptide nanofiber hydrogel H9e, when combined with the PRRSV MLV vaccine, can enhance vaccine efficacy against two different PRRSV strains by modulating both host humoral and cellular immune responses. PMID:23933333

The potential impact of a prophylactic vaccine for human papillomavirus on the current cervical screening programme in Hong Kong.

PubMed

Koljonen, Paul A

2007-08-01

To review and summarise current controversies in cervical screening in Hong Kong and discuss the potential impact of prophylactic human papillomavirus vaccination. Literature search of Medline to December 2006, the Hong Kong Cancer Registry, and Centre of Disease Control. Key words search terms were: 'human papillomavirus', 'vaccine', 'cervical cancer', 'screening programme', and 'Hong Kong'. Original articles, review papers, books, and the worldwide web. Cervical cancer is one of the most common cancers in Hong Kong, and can be prevented if detected at its pre-cancerous stage. Despite the huge disease burden this imposes on our society and robust advocacy by the academic sector, an appropriate screening programme is still not in place. Existence of a vaccine that could potentially reduce the costs of universal screening should prompt our government to re-consider subsidising such a programme. While a combined screening-vaccination programme may be more cost-effective than screening alone, the vaccine is still costly, and the government must consider all the pros and cons. The new human papillomavirus vaccine, combined with an organised screening programme, is probably a more cost-effective way of preventing morbidity and mortality due to cervical cancer than the current programme in Hong Kong. More research and cost-effectiveness analyses are needed to decide on the ideal ages for primary vaccination and the requirement for booster shots.

Hepatitis E virus: Current epidemiology and vaccine.

PubMed

Wu, Xing; Chen, Pan; Lin, Huijuan; Hao, Xiaotian; Liang, Zhenglun

2016-10-02

Hepatitis E virus infections have been continuously reported in Indian subcontinent, Africa, southeast and central Asia, posing great health threats to the public, especially to pregnant women. Hecolin® is the only licensed HEV vaccine developed by Xiamen Innovax Biotech Co., Ltd. Extensive characterizations on antigenicity, physicochemical properties, efficacy in clinical trials, and manufacturing capability have made Hecolin® a promising vaccine for HEV control. However, there are many obstacles in large scale application of Hecolin®. Efforts are needed to further evaluate safety and efficacy in HEV risk populations, and to complement HEV standards for quality control. Passing World Health Organization prequalification and licensing outside China are priorities as these are also hindering Hecolin® promotion. Multilateral cooperation among Chinese vaccine manufacturers, Chinese National Regulatory Authorization (NRA) and WHO will expedite the entrance of Hecolin® into international market, so that Hecolin® could play its due role in global hepatitis E control.

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

PubMed Central

Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

2016-01-01

Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

PubMed

Zhang, Lu; Ru, Huan-Wei; Chen, Fu-Zeng; Jin, Chun-Yan; Sun, Rui-Feng; Fan, Xiao-Yong; Guo, Ming; Mai, Jun-Tao; Xu, Wen-Xi; Lin, Qing-Xia; Liu, Jun

2016-02-01

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.

Considerations on the current universal vaccination policy against hepatitis A in Greece after recent outbreaks.

PubMed

Mellou, Kassiani; Sideroglou, Theologia; Papaevangelou, Vassiliki; Katsiaflaka, Anna; Bitsolas, Nikolaos; Verykouki, Eleni; Triantafillou, Eleni; Baka, Agoritsa; Georgakopoulou, Theano; Hadjichristodoulou, Christos

2015-01-01

Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country's total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods.

Genetic engineering of live attenuated influenza viruses.

PubMed

Jin, Hong; Chen, Zhongying; Liu, Jonathan; Kemble, George

2012-01-01

The first live attenuated influenza vaccine (LAIV) was licensed in the USA in 2003; it is a trivalent vaccine composed of two type A (H1N1 and H3N2) and one type B influenza virus each at 10(7) fluorescent focus units (FFU). Each influenza vaccine strain is a reassortant virus that contains the hemagglutinin (HA) and neuraminidase (NA) gene segments from a wild-type influenza virus and the six internal protein gene segments from a master donor virus (MDV) of either cold-adapted A/Ann Arbor/6/60 or B/Ann Arbor/1/66. MDV confers the cold-adapted, temperature-sensitive, and attenuation phenotypes to the vaccine strains. The reassortant vaccine seeds are currently produced by reverse genetics and amplified in specific pathogen-free (SPF) 9-11 days old embryonated chicken eggs for manufacture. In addition, MDCK cell culture manufacture processes have been developed to produce LAIV for research use and with modifications for clinical and/or commercial grade material production.

Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine constructed by reverse genetic manipulation

PubMed Central

Wen, Feng; Ma, Ji-Hong; Yang, Fu-Ru; Huang, Meng; Zhou, Yan-Jun; Li, Ze-Jun

2014-01-01

Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China. PMID:24675833

Validation of current procedural terminology codes for rotavirus vaccination among infants in two commercially insured US populations.

PubMed

Hoffman, Veena; Everage, Nicholas J; Quinlan, Scott C; Skerry, Kathleen; Esposito, Daina; Praet, Nicolas; Rosillon, Dominique; Holick, Crystal N; Dore, David D

2016-12-01

We validated procedure codes used in health insurance claims for reimbursement of rotavirus vaccination by comparing claims for monovalent live-attenuated human rotavirus vaccine (RV1) and live, oral pentavalent rotavirus vaccine (RV5) to medical records. Using administrative data from two commercially insured United States populations, we randomly sampled vaccination claims for RV1 and RV5 from a cohort of infants aged less than 1 year from an ongoing post-licensure safety study of rotavirus vaccines. The codes for RV1 and RV5 found in claims were confirmed through medical record review. The positive predictive value (PPV) of the Current Procedural Terminology codes for RV1 and RV5 was calculated as the number of medical record-confirmed vaccinations divided by the number of medical records obtained. Medical record review confirmed 92 of 104 RV1 vaccination claims (PPV: 88.5%; 95% CI: 80.7-93.9%) and 98 of 113 RV5 vaccination claims (PPV: 86.7%; 95% CI: 79.1-92.4%). Among the 217 medical records abstracted, only three (1.4%) of vaccinations were misclassified in claims-all were RV5 misclassified as RV1. The medical records corresponding to 9 RV1 and 15 RV5 claims contained insufficient information to classify the type of rotavirus vaccine. Misclassification of rotavirus vaccines is infrequent within claims. The PPVs reported here are conservative estimates as those with insufficient information in the medical records were assumed to be incorrectly coded in the claims. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

PubMed

Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

2018-02-14

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

Global genetic diversity of the Plasmodium vivax transmission-blocking vaccine candidate Pvs48/45.

PubMed

Vallejo, Andres F; Martinez, Nora L; Tobon, Alejandra; Alger, Jackeline; Lacerda, Marcus V; Kajava, Andrey V; Arévalo-Herrera, Myriam; Herrera, Sócrates

2016-04-12

Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity, suggesting its potential as a P. vivax transmission-blocking vaccine candidate. To determine sequence polymorphism of natural parasite isolates and its potential influence on the protein structure, all pvs48/45 sequences reported in databases from around the world as well as those from low-transmission settings of Latin America were compared. Plasmodium vivax parasite isolates from malaria-endemic regions of Colombia, Brazil and Honduras (n = 60) were used to sequence the Pvs48/45 gene, and compared to those previously reported to GenBank and PlasmoDB (n = 222). Pvs48/45 gene haplotypes were analysed to determine the functional significance of genetic variation in protein structure and vaccine potential. Nine non-synonymous substitutions (E35K, Y196H, H211N, K250N, D335Y, E353Q, A376T, K390T, K418R) and three synonymous substitutions (I73, T149, C156) that define seven different haplotypes were found among the 282 isolates from nine countries when compared with the Sal I reference sequence. Nucleotide diversity (π) was 0.00173 for worldwide samples (range 0.00033-0.00216), resulting in relatively high diversity in Myanmar and Colombia, and low diversity in Mexico, Peru and South Korea. The two most frequent substitutions (E353Q: 41.9 %, K250N: 39.5 %) were predicted to be located in antigenic regions without affecting putative B cell epitopes or the tertiary protein structure. There is limited sequence polymorphism in pvs48/45 with noted geographical clustering among Asian and American isolates. The low genetic diversity of the protein does not influence the predicted antigenicity or protein structure and, therefore

Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

PubMed Central

Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

2014-01-01

Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

Negative impact of prior influenza vaccination on current influenza vaccination among people infected and not infected in prior season: A test-negative case-control study in Japan.

PubMed

Saito, Nobuo; Komori, Kazuhiro; Suzuki, Motoi; Morimoto, Kounosuke; Kishikawa, Takayuki; Yasaka, Takahiro; Ariyoshi, Koya

2017-01-23

Accumulating evidences indicate that repeated influenza vaccination has negative impact on the vaccine effectiveness (VE). However no published studies considered past influenza infection when assessing the VE of repeated vaccination. Prospective surveillance was conducted from 2009 to 2012 at a community hospital on a small island in Japan. The study included all outpatients with an influenza-like illness (ILI) who attended the hospital, and a rapid diagnostic test (RDT) was used to diagnose influenza A/B infection. The VE of trivalent inactivated influenza vaccine (TIV) against medically attended influenza A (MA-fluA) was estimated using a test-negative case-control study design. The influence of TIV in the prior season on VE in the current season was investigated in the context of MA-fluA during the prior season. During the three influenza seasons, 5838 ILI episodes (4127 subjects) were analysed. Subjects who had an episode of MA-fluA in the prior season were at a significantly lower risk of MA-fluA in the current season (adjusted odds ratio: 0.38, 95% CI: 0.30-0.50). The overall adjusted VE was 28% (95% CI, 14-40). VE was substantially lower in subjects vaccinated in the prior season compared to those who had not been vaccinated in prior season (19%; 95% CI: 0-35 vs 46%; 95% CI: 26-60, test for interaction, P value <0.05). In subjects who did not have MA-fluA in the prior season showed the attenuation of VE due to repeated vaccination (13%; 95% CI: -7 to 30 vs 44%; 95% CI: 24-59, test for interaction, P<0.05). However this effect was not detected in subjects who had contracted MA-fluA in the prior season. Negative effects of repeated vaccination were significant among those without history of MA-fluA in the prior season. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Live attenuated vaccines: Historical successes and current challenges.

PubMed

Minor, Philip D

2015-05-01

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

HIV Vaccines

MedlinePlus

... an NIH-supported clinical trial was launched to test a modified HIV vaccine. This current vaccine trial, called HVTN 702, is testing whether an experimental vaccine regimen safely prevents HIV infection among South African adults. Learn more in this blog post and in the video below. /* // ** // */ Why Do We ...

Childhood Vaccine Schedule

MedlinePlus

... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

Vaccines Stop Illness

MedlinePlus

Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

Evidence for viral virulence as a predominant factor limiting human immunodeficiency virus vaccine efficacy.

PubMed

Mooij, P; Bogers, W M; Oostermeijer, H; Koornstra, W; Ten Haaft, P J; Verstrepen, B E; Van Der Auwera, G; Heeney, J L

2000-05-01

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian/human immunodeficiency virus (SHIV) challenge experiments in HIV-1 subunit-vaccinated rhesus macaques. Of a total of 22 animals, 10 nonimmunized animals served as controls; the remainder were vaccinated with the CCR5 binding envelope of HIV-1(W6.1D). In the first study, heterologous challenge included two nonpathogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1(han2) and HIV-1(sf13) strains. In the second study, all immunized animals were rechallenged with SHIV(89. 6p), a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIV(sf13) or SHIV(han2) challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV(89.6p), protection was achieved in only one of the previously protected vaccinees. A secondary but beneficial effect of immunization on virus load and CD4(+) T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these results suggest the importance of developing vaccine strategies capable of protecting from particularly virulent variants of HIV-1.

Current Status of Syphilis Vaccine Development: Need, Challenges, Prospects

PubMed Central

Cameron, Caroline E.; Lukehart, Sheila A.

2013-01-01

Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community’s accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

PubMed

Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

2014-12-01

Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1. © 2014 John Wiley & Sons Ltd.

The Bulgarian vaccine Crimean-Congo haemorrhagic fever virus strain.

PubMed

Papa, Anna; Papadimitriou, Evangelia; Christova, Iva

2011-03-01

The Crimean-Congo haemorrhagic fever virus (CCHFV) is a 3-segmented RNA virus, which causes disease with a high fatality rate in humans. An inactivated suckling mouse brain-derived vaccine is used in Bulgaria for protection against CCHF. Strain V42/81 is currently used for the vaccine preparation. As the M-RNA segment plays a major role in the immune response, the full-length M segment sequence of the V42/81 strain was characterized. A great genetic diversity was observed among CCHFV strains. In order to gain an insight into the topology of the strain in the CCHFV phylogenetic trees, the full-length S and partial L segments were additionally sequenced and analyzed.

Measles vaccination: Threat from related veterinary viruses and need for continued vaccination post measles eradication.

PubMed

Cosby, Sara Louise; Weir, Leanne

2018-01-02

Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and animal species. They confer diseases which have contributed to morbidity and mortality of the population on a global scale. There is substantial evidence from both natural and experimental infections that morbilliviruses can readily cross species barriers. Of most concern with regard to zoonosis is the more recently reported fatal infection of primates in Japan and China with strains of CDV which have adapted to this host. The close genetic relationship, shared cell entry receptors and similar pathogenesis between the morbilliviruses highlights the potential consequences of complete withdrawal of MV vaccination after eradication. Therefore, it would be prudent to continue the current MV vaccination. Ultimately development of novel, safe vaccines which have higher efficacy against the veterinary morbilliviruses is a priority. These would to protect the human population long term against the threat of zoonosis by these veterinary viruses.

In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

PubMed

Pfaff, Florian; Müller, Thomas; Freuling, Conrad M; Fehlner-Gardiner, Christine; Nadin-Davis, Susan; Robardet, Emmanuelle; Cliquet, Florence; Vuta, Vlad; Hostnik, Peter; Mettenleiter, Thomas C; Beer, Martin; Höper, Dirk

2018-02-10

Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection. Copyright © 2018. Published by Elsevier Ltd.

Rheumatoid arthritis and Swine influenza vaccine: a case report.

PubMed

Basra, Gurjot; Jajoria, Praveen; Gonzalez, Emilio

2012-01-01

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

PubMed

Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

2015-12-30

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. Copyright © 2016. Published by Elsevier Ltd.

Viruses - from pathogens to vaccine carriers.

PubMed

Small, Juliana C; Ertl, Hildegund C J

2011-10-01

Vaccination is mankind's greatest public health success story. By now vaccines to many of the viruses that once caused fatal childhood diseases are routinely used throughout the world. Traditional methods of vaccine development through inactivation or attenuation of viruses have failed for some of the most deadly human pathogens, necessitating new approaches. Genetic modification of viruses not only allows for their attenuation but also for incorporation of sequences from other viruses, turning one pathogen into a vaccine carrier for another. Recombinant viruses have pros and cons as vaccine carriers, as discussed below using vectors based on adenovirus, herpesvirus, flavivirus, and rhabdovirus as examples.

Considerations on the Current Universal Vaccination Policy against Hepatitis A in Greece after Recent Outbreaks

PubMed Central

Mellou, Kassiani; Sideroglou, Theologia; Papaevangelou, Vassiliki; Katsiaflaka, Anna; Bitsolas, Nikolaos; Verykouki, Eleni; Triantafillou, Eleni; Baka, Agoritsa; Georgakopoulou, Theano; Hadjichristodoulou, Christos

2015-01-01

Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country’s total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods. PMID:25590132

Vaccines: an ongoing promise?

PubMed

Alsahli, M; Farrell, R J; Michetti, P

2001-01-01

Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

Ten years of PCV2 vaccines and vaccination: Is eradication a possibility?

PubMed

Afghah, Zahra; Webb, Brett; Meng, Xiang-Jin; Ramamoorthy, Sheela

2017-07-01

More than two decades after its emergence, porcine circovirus type 2 (PCV2) remains an economically important swine pathogen. Commercial vaccines which were first introduced to the U.S in 2006, have been highly effective in reducing clinical signs and improving production. Recent studies have indicated a declining level of PCV2 prevalence and viremia in the field. However, reports on the emergence of new viral variants have also continued to increase. This article reviews topics of current interest in the field of PCV2 vaccines; including the comparative efficacy of the available commercial products, efficacy of current vaccines against new and emerging strains, findings on the differences between immunity in natural infection versus vaccination, limitations of current experimental models for PCV2 vaccine studies, and new developments in novel experimental vaccines. The discussion is framed in the context of attempts for the possible eradication of PCV2 in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Governments, off-patent vaccines, smallpox and universal childhood vaccination.

PubMed

Music, Stanley

2010-01-22

WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden.

Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

PubMed

Silva, José V J; Lopes, Thaísa R R; Oliveira-Filho, Edmilson F de; Oliveira, Renato A S; Durães-Carvalho, Ricardo; Gil, Laura H V G

2018-06-01

Emerging and re-emerging viral infections transmitted by insect vectors (arthopode-borne viruses, arbovirus) are a serious threat to global public health. Among them, yellow fever (YFV), dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses are particularly important in tropical and subtropical regions. Although vector control is one of the most used prophylactic measures against arboviruses, it often faces obstacles, such as vector diversity, uncontrolled urbanization and increasing resistance to insecticides. In this context, vaccines may be the best control strategy for arboviral diseases. Here, we provide a general overview about licensed vaccines and the most advanced vaccine candidates against YFV, DENV, CHIKV and ZIKV. In particular, we highlight vaccine difficulties, the current status of the most advanced strategies and discuss how the molecular characteristics of each virus can influence the choice of the different vaccine formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

[VACCINES].

PubMed

Bellver Capella, Vincente

2015-10-01

Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

Edible vaccines against veterinary parasitic diseases--current status and future prospects.

PubMed

Jacob, Siju S; Cherian, Susan; Sumithra, T G; Raina, O K; Sankar, M

2013-04-08

Protection of domestic animals against parasitic infections remains a major challenge in most of the developing countries, especially in the surge of drug resistant strains. In this circumstance vaccination seems to be the sole practical strategy to combat parasites. Most of the presently available live or killed parasitic vaccines possess many disadvantages. Thus, expression of parasitic antigens has seen a continued interest over the past few decades. However, only a limited success was achieved using bacterial, yeast, insect and mammalian expression systems. This is witnessed by an increasing number of reports on transgenic plant expression of previously reported and new antigens. Oral delivery of plant-made vaccines is particularly attractive due to their exceptional advantages. Moreover, the regulatory burden for veterinary vaccines is less compared to human vaccines. This led to an incredible investment in the field of transgenic plant vaccines for veterinary purpose. Plant based vaccine trials have been conducted to combat various significant parasitic diseases such as fasciolosis, schistosomosis, poultry coccidiosis, porcine cycticercosis and ascariosis. Besides, passive immunization by oral delivery of antibodies expressed in transgenic plants against poultry coccidiosis is an innovative strategy. These trials may pave way to the development of promising edible veterinary vaccines in the near future. As the existing data regarding edible parasitic vaccines are scattered, an attempt has been made to assemble the available literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

PubMed

Martínez-Baz, Iván; Casado, Itziar; Navascués, Ana; Díaz-González, Jorge; Aguinaga, Aitziber; Barrado, Laura; Delfrade, Josu; Ezpeleta, Carmen; Castilla, Jesús

2017-03-15

The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Rotavirus vaccines

PubMed Central

Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Lopman, Benjamin; Fleming, Jessica; Lewis, Kristen; Jiang, Baoming; Gentsch, Jon; Steele, Duncan; Parashar, Umesh D

2011-01-01

Early rotavirus vaccine adopter countries in the Americas, Europe, and in Australia have documented substantial declines in rotavirus disease burden following the introduction of vaccination. However, the full public health impact of rotavirus vaccines has not been realized as they have not been introduced into routine immunization programs in countries of Africa and Asia with the highest rotavirus disease morbidity and mortality burden. In this article, we review the epidemiology of rotavirus disease, the development and current status of rotavirus vaccines including newly available vaccine impact data from early-introducer countries, and future priorities for implementation and monitoring of rotavirus vaccination programs in developing countries. PMID:22108032

Overview of Vaccine Adjuvants: Introduction, History, and Current Status.

PubMed

Shah, Ruchi R; Hassett, Kimberly J; Brito, Luis A

2017-01-01

Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

PubMed Central

Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

2015-01-01

Background No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. Methodology/Principal Findings The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. Significance VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection

Current status of syphilis vaccine development: need, challenges, prospects.

PubMed

Cameron, Caroline E; Lukehart, Sheila A

2014-03-20

Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community's accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

Recently Patented Viral Nucleotide Sequences and Generation of Virus-Derived Vaccines.

PubMed

Venkataraman, Srividhya; Ahmad, Tauqeer; Haidar, Mounir A; Hefferon, Kathleen L

2017-01-01

With an increase in comprehension of the molecular biology of viruses, there has been a recent surge in the application of virus sequences and viral gene expression strategies towards the diagnosis and treatment of diseases. The scope of the patenting landscape has widened as a result and the current review discusses patents pertaining to live / attenuated viral vaccines. The vaccines addressed here have been developed by both conventional means as well as by the state-of-the-art genetic engineering techniques. This review also addresses the applications of these patents for clinical and biotechnological purposes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

MyD88/CD40 Genetic Adjuvant Function in Cutaneous Atypical Antigen-Presenting Cells Contributes to DNA Vaccine Immunogenicity

PubMed Central

Slawin, Kevin M.; Levitt, Jonathan M.; Spencer, David M.

2016-01-01

Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways. When incorporated into a DNA vaccine, signaling by the MC adjuvant increased antigen-specific CD8+ T cells and promoted elimination of pre-established tumors. Interestingly, MC-enhanced vaccine efficacy did not require direct-expression of either antigen or adjuvant by local antigen-presenting cells, but rather our data supports a key role for MC function in “atypical” antigen-presenting cells of skin. In particular, MC adjuvant-modified keratinocytes increased inflammatory cytokine secretion, upregulated surface MHC class I, and were able to increase in vitro and in vivo priming of antigen-specific CD8+ T cells. Furthermore, in the absence of critical CD8α+/CD103+ cross-priming dendritic cells, MC was still able to promote immune priming in vivo, albeit at a reduced level. Altogether, our data support a mechanism by which MC signaling activates an inflammatory phenotype in atypical antigen-presenting cells within the cutaneous vaccination site, leading to an enhanced CD8+ T cell response against DNA vaccine-encoded antigens, through both CD8α+/CD103+ dendritic cell-dependent and independent pathways. PMID:27741278

Vaccine-preventable diseases, vaccines and Guillain-Barre' syndrome.

PubMed

Principi, Nicola; Esposito, Susanna

2018-06-04

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy. Infections and vaccines have been hypothesized to play a role in triggering GBS development. These beliefs can play a role in reducing vaccination coverage. In this report, data concerning this hypothesis are discussed. It is shown that an association between vaccine administration and GBS has never been proven for most of debated vaccines, although it cannot be definitively excluded. The only exception is the influenza vaccine, at least for the preparation used in 1976. For some vaccines, such as measles/mumps/rubella, human papillomavirus, tetravalent conjugated meningococcal vaccine, and influenza, the debate between supporters and opponents of vaccination remains robust and perception of vaccines' low safety remains a barrier to achieving adequate vaccination coverage. Less than 1 case of GBS per million immunized persons might occur for these vaccines. However, in some casesimmunization actually reduces the risk of GBS development. In addition, the benefits of vaccination are clearly demonstrated by the eradication or enormous decline in the incidence of many vaccine-preventable diseases. These data highlight that the hypothesized risks of adverse events, such as GBS, cannot be considered a valid reason to avoid the administration of currently recommended vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epilepsy and vaccinations: Italian guidelines.

PubMed

Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto

2013-10-01

Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Status of vaccine research and development of vaccines for HIV-1.

PubMed

Safrit, Jeffrey T; Fast, Patricia E; Gieber, Lisa; Kuipers, Hester; Dean, Hansi J; Koff, Wayne C

2016-06-03

Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus-infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof-of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Use of Prior Vaccinations for the Development of New Vaccines

NASA Astrophysics Data System (ADS)

Etlinger, H. M.; Gillessen, D.; Lahm, H.-W.; Matile, H.; Schonfeld, H.-J.; Trzeciak, A.

1990-07-01

There is currently a need for vaccine development to improve the immunogenicity of protective epitopes, which themselves are often poorly immunogenic. Although the immunogenicity of these epitopes can be enhanced by linking them to highly immunogenic carriers, such carriers derived from current vaccines have not proven to be generally effective. One reason may be related to epitope-specific suppression, in which prior vaccination with a protein can inhibit the antibody response to new epitopes linked to the protein. To circumvent such inhibition, a peptide from tetanus toxoid was identified that, when linked to a B cell epitope and injected into tetanus toxoid-primed recipients, retained sequences for carrier but not suppressor function. The antibody response to the B cell epitope was enhanced. This may be a general method for taking advantage of previous vaccinations in the development of new vaccines.

The global fight to develop antipoverty vaccines in the anti-vaccine era.

PubMed

Hotez, Peter J

2018-02-02

Antipoverty vaccines are the vaccines targeting a group of approximately 20 neglected tropical diseases (NTDs), as currently defined by the World Health Organization (WHO). The "antipoverty" moniker refers to the fact that NTDs trap populations in poverty due to their chronic and deleterious effects on child intellect and worker productivity. Therefore, NTD vaccines can be expected to promote both global health and economic advancement. Unfortunately, antipoverty vaccine development has lagged behind vaccines for major childhood infections and pandemic threats, despite evidence for their cost-effectiveness and cost-savings. Currently, the only licensed vaccines for NTDs include those for yellow fever, dengue, and rabies, although several other NTD vaccines for hookworm disease, schistosomiasis, leishmaniasis, and Zika and Ebola virus infections are in different stages of clinical development, while others are at the preclinical development stage. With the exception of the viral NTD vaccines there so far has been minimal industry interest in the antipoverty vaccines, leaving their development to a handful of non-profit product development partnerships. The major scientific and geopolitical hurdles to antipoverty vaccine development are discussed, including a rising antivaccine ("antivax") movement now entering highly populated low- and middle-income countries.

Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

PubMed

Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

2017-01-01

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Ab-initio conformational epitope structure prediction using genetic algorithm and SVM for vaccine design.

PubMed

Moghram, Basem Ameen; Nabil, Emad; Badr, Amr

2018-01-01

T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95

Vaccination of carp against SVCV with an oral DNA vaccine or an insect cells-based subunit vaccine.

PubMed

Embregts, C W E; Rigaudeau, D; Tacchi, L; Pijlman, G P; Kampers, L; Veselý, T; Pokorová, D; Boudinot, P; Wiegertjes, G F; Forlenza, M

2018-03-19

We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Heritability of vaccine-induced measles neutralizing antibody titers.

PubMed

Schaid, Daniel J; Haralambieva, Iana H; Larrabee, Beth R; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

2017-03-07

Understanding how genetics influences inter-individual variation of antibody titers in response to measles vaccination is vital to understanding possible sources of vaccine failure as well as improved vaccine development. Although it is recognized that both the human leukocyte antigen (HLA) genes and the immunoglobulin allotype genes play significant roles in immune response, there is significant variation in antibody titers that is not explained by these genes. To obtain a more complete estimate of the role of the entire genome, we used a large panel of single nucleotide polymorphisms to estimate the heritability of antibody response to measles vaccine. Based on 935 subjects with European ancestry, we estimated the heritability to be 49% (standard error 0.17). We also estimated the heritability attributable to each chromosome, and found a large range in chromosome-specific heritabilities. Notably, chromosome 1 had the largest estimate (28%), while chromosome 6, which harbors HLA, had an estimated heritability of 13%. Compared with a prior study of twins in the same community, which resulted in a heritability estimate of 88.5%, our study suggests there are either many rare genetic variants, or many common genetic variants of small effect sizes that contribute to variations of antibody titers in response to measles vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anthrax vaccination strategies

PubMed Central

Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

2009-01-01

The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

The effects of anti-vaccine conspiracy theories on vaccination intentions.

PubMed

Jolley, Daniel; Douglas, Karen M

2014-01-01

The current studies investigated the potential impact of anti-vaccine conspiracy beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination intentions. In Study 1, British parents completed a questionnaire measuring beliefs in anti-vaccine conspiracy theories and the likelihood that they would have a fictitious child vaccinated. Results revealed a significant negative relationship between anti-vaccine conspiracy beliefs and vaccination intentions. This effect was mediated by the perceived dangers of vaccines, and feelings of powerlessness, disillusionment and mistrust in authorities. In Study 2, participants were exposed to information that either supported or refuted anti-vaccine conspiracy theories, or a control condition. Results revealed that participants who had been exposed to material supporting anti-vaccine conspiracy theories showed less intention to vaccinate than those in the anti-conspiracy condition or controls. This effect was mediated by the same variables as in Study 1. These findings point to the potentially detrimental consequences of anti-vaccine conspiracy theories, and highlight their potential role in shaping health-related behaviors.

Oral vaccination against plague using Yersinia pseudotuberculosis.

PubMed

Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth

2017-04-01

Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Novel vaccines against influenza viruses

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

2011-01-01

Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination. PMID:21968298

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

PubMed

Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

2017-01-01

Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

Generation of a More Immunogenic Measles Vaccine by Increasing Its Hemagglutinin Expression

PubMed Central

Julik, Emily

2016-01-01

ABSTRACT Imported measles virus (MV) outbreaks are maintained by poor vaccine responders and unvaccinated people. A convenient but more immunogenic vaccination strategy would enhance vaccine performance, contributing to measles eradication efforts. We report here the generation of alternative pediatric vaccines against MV with increased expression of the H protein in the background of the current MV vaccine strain. We generated two recombinants: MVvac2-H2, with increased full-length H expression resulting in a 3-fold increase in H incorporation into virions, and MVvac2-Hsol, vectoring a truncated, soluble form of the H protein that is secreted into the supernatants of infected cells. Replication fitness was conserved despite the duplication of the H cistron for both vectors. The modification to the envelope of MVvac2-H2 conferred upon this virus a measurable level of resistance to in vitro neutralization by MV polyclonal immune sera without altering its thermostability. Most interestingly, both recombinant MVs with enhanced H expression were significantly more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic after a single, human-range dose in genetically modified MV-susceptible mice. IMPORTANCE Measles incidence was reduced drastically following the introduction of attenuated vaccines, but progress toward the eradication of this virus has stalled, and MV still threatens unvaccinated populations. Due to the contributions of primary vaccine failures and too-young-to-be-vaccinated infants to this problem, more immunogenic measles vaccines are highly desirable. We generated two experimental MV vaccines based on a current vaccine's genome but with enriched production of the H protein, the main MV antigen in provoking immunity. One vaccine incorporated H at higher rates in the viral envelope, and the other secreted a soluble H protein from infected cells. The increased expression of H by these vectors improved

Rotavirus vaccines

PubMed Central

Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

2014-01-01

Rotavirus is the leading cause of severe diarrhea among children <5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

Foot and mouth disease vaccine strain selection: Current approaches and future perspectives.

PubMed

Mahapatra, Mana; Parida, Satya

2018-06-27

Lack of cross protection between foot and mouth disease (FMD) virus (FMDV) serotypes as well as incomplete protection between some subtypes of FMDV affect the application of vaccine in the field. Further, the emergence of new variant FMD viruses periodically makes the existing vaccine inefficient. Consequently, periodical vaccine strain selection either by in vivo methods or in vitro methods become an essential requirement to enable utilisation of appropriate and efficient vaccines. Areas covered: Here we describe the cross reactivity of the existing vaccines with the global pool of circulating viruses and the putative selected vaccine strains for targeting protection against the two major circulating serotype O and A FMD viruses for East Africa, the Middle East, South Asia and South East Asia. Expert Commentary: Although in vivo cross protection studies are more appropriate methods for vaccine matching and selection than in vitro neutralisation test or ELISA, in the face of an outbreak both in vivo and in vitro methods of vaccine matching are not easy, and time consuming. The FMDV capsid contains all the immunogenic epitopes, and therefore vaccine strain prediction models using both capsid sequence and serology data will likely replace existing tools in the future.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

PubMed

Doroshenko, Alexander; Halperin, Scott A

2009-06-01

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

Economic impact of thermostable vaccines.

PubMed

Lee, Bruce Y; Wedlock, Patrick T; Haidari, Leila A; Elder, Kate; Potet, Julien; Manring, Rachel; Connor, Diana L; Spiker, Marie L; Bonner, Kimberly; Rangarajan, Arjun; Hunyh, Delphine; Brown, Shawn T

2017-05-25

While our previous work has shown that replacing existing vaccines with thermostable vaccines can relieve bottlenecks in vaccine supply chains and thus increase vaccine availability, the question remains whether this benefit would outweigh the additional cost of thermostable formulations. Using HERMES simulation models of the vaccine supply chains for the Republic of Benin, the state of Bihar (India), and Niger, we simulated replacing different existing vaccines with thermostable formulations and determined the resulting clinical and economic impact. Costs measured included the costs of vaccines, logistics, and disease outcomes averted. Replacing a particular vaccine with a thermostable version yielded cost savings in many cases even when charging a price premium (two or three times the current vaccine price). For example, replacing the current pentavalent vaccine with a thermostable version without increasing the vaccine price saved from $366 to $10,945 per 100 members of the vaccine's target population. Doubling the vaccine price still resulted in cost savings that ranged from $300 to $10,706, and tripling the vaccine price resulted in cost savings from $234 to $10,468. As another example, a thermostable rotavirus vaccine (RV) at its current (year) price saved between $131 and $1065. Doubling and tripling the thermostable rotavirus price resulted in cost savings ranging from $102 to $936 and $73 to $808, respectively. Switching to thermostable formulations was highly cost-effective or cost-effective in most scenarios explored. Medical cost and productivity savings could outweigh even significant price premiums charged for thermostable formulations of vaccines, providing support for their use. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rabies vaccination compliance following introduction of the triennial vaccination interval--the Texas experience.

PubMed

Rogers, C L

2011-06-01

In 2003 the Texas Board of Health approved a modification to the Texas Administrative Code that permitted pet owners to have their dogs (Canis familiaris) and cats (Felis catus) vaccinated against rabies every 3 years, provided a triennial vaccine was used. The change had been opposed by hundreds in the veterinary community, some concerned that its implementation would be followed by a decrease in rabies vaccination rates. To determine if this decrease had occurred, rabies vaccination rates for 4 years before and after migration to the 3-year vaccination interval were examined. Data for dogs and cats, ≥ 4 months of age, were collected from the Texas Department of Health Rabies Incident Report database. Each animal's record included its current rabies vaccination status. The number of animals that were currently vaccinated against rabies was tallied and the percent vaccinated was calculated. From 1999 through 2002, 46% of dogs were vaccinated against rabies. From 2004 through 2007, 56% of dogs were vaccinated against rabies. From 1999 to 2002, 18% of cats were vaccinated against rabies. From 2004 to 2007, 30% of cats were vaccinated against rabies. There has been a significant increase in the numbers of dogs (P < 0.001), and cats (P < 0.001), vaccinated against rabies since the introduction of the triennial vaccination interval. This observational study documents the positive changes in rabies vaccination rates following migration from a 1-year to 3-year vaccination interval. © 2010 Blackwell Verlag GmbH.

A systematic review of genetic diversity of human rotavirus circulating in South Korea.

PubMed

Than, Van Thai; Jeong, Sunyoung; Kim, Wonyong

2014-12-01

Rotavirus infections continue to be the leading cause of severe diarrhea in young Korean children. Rotavirus data acquired from uninterrupted surveillance studies between 1989 and 2009 in South Korea were analyzed to better understand the genetic diversity and evolution. The relationship between rotaviruses and the currently licensed rotavirus vaccine viruses was also examined. The most prevalent rotavirus strains, with genotype G1P[8], followed by G3P[8], G4P[6], and G2P[4], accounted for approximately 76.7% of the total identified strains, and more recently, rotavirus G9P[8] has significance increased to be the fifth most common genotype. Phylogenetic analyses underscored the heterogeneity between viral populations within each genotype, with different lineages and sub-lineages. Although the currently licensed rotavirus vaccines are effective, safe, and economical, additional data from rotavirus monitoring is necessary to evaluate the efficacy of these vaccines for their sustained use in South Korea. The present study provides comprehensive and up-to-date information regarding the epidemiology, genetic diversity, and evolution of the circulating rotaviruses in South Korea. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Human papillomavirus vaccination of males: attitudes and perceptions of physicians who vaccinate females.

PubMed

Weiss, Thomas W; Zimet, Gregory D; Rosenthal, Susan L; Brenneman, Susan K; Klein, Jonathan D

2010-07-01

We assessed U.S. physicians' attitudes and perceptions regarding potential human papillomavirus (HPV) vaccination of males. We surveyed a random sample of 2,714 pediatricians and family practitioners identified in administrative claims of a U.S. health plan as HPV vaccinators of females; 595 pediatricians and 499 family practitioners participated. Most physicians would recommend HPV vaccination to males aged 11-12 (63.9%), 13-18 (93.4%), and 19-26 (92.7%) years. Physicians agreed that males should be vaccinated to prevent them from getting genital and anal warts (52.9% strongly and 36.0% somewhat) and to protect females from cervical cancer (75.3% strongly and 20.8% somewhat). Physicians agreed that an HPV vaccine recommendation for males would increase opportunities to discuss sexual health with adolescent male patients (58.7% strongly, 35.3% somewhat). Most did not strongly agree (15.4% strongly, 45.4% somewhat) that parents of adolescent male patients would be interested in HPV vaccination for males, that a gender-neutral HPV vaccine recommendation would increase acceptance by adolescent females and their parents (19.6% strongly, 42.0% somewhat), or that a gender-neutral recommendation would improve current female vaccination rates (10.4% strongly, 26.0% somewhat). Physicians who currently vaccinate females against HPV supported the concept of vaccinating males for its benefits for both sexes. They agreed that a gender-neutral HPV vaccination recommendation would be appropriate with regard to public health and believed that it would increase opportunities for sexual health discussions, but were less sure that such a recommendation would change patient or parental attitudes toward HPV vaccination or improve current HPV vaccination efforts. Copyright (c) 2010 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain

PubMed Central

Castilla, Jesús; Pozo, Francisco

2017-01-01

Background Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. PMID:28614376

Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture

PubMed Central

Rajão, Daniela S.; Pérez, Daniel R.

2018-01-01

Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses. Efforts toward overcoming these challenges aim at improving the strength and/or breadth of the immune response. Novel vaccine technologies, the so-called universal vaccines, focus on stimulating better cross-protection against many or all influenza strains. However, vaccine platforms or manufacturing technologies being tested to improve vaccine efficacy are heterogeneous between different species and/or either tailored for epidemic or pandemic influenza. Here, we discuss current vaccines to protect humans and animals against influenza, highlighting challenges faced to effective and uniform novel vaccination strategies and approaches. PMID:29467737

Replication of Rubella Vaccine Population Genetic Studies: Validation of HLA Genotype and Humoral Response Associations

PubMed Central

Ovsyannikova, Inna G.; Jacobson, Robert M.; Vierkant, Robert A.; O’Byrne, Megan M.; Poland, Gregory A.

2009-01-01

Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12–18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11–19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p=0.028; 2nd cohort 20.5 IU/ml, p=0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p=0.048; 2nd cohort 25.8 IU/ml, p=0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml, p=0.021; 2nd cohort 36.2 IU/ml, p=0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p=0.011; 2nd cohort 21.4 IU/ml, p=0.032) and DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1 IU/ml, p=0.023) haplotypes with lower rubella-specific antibodies were observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses. PMID:19761839

Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

PubMed

Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

2004-01-26

The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

17D yellow fever vaccines: new insights. A report of a workshop held during the World Congress on medicine and health in the tropics, Marseille, France, Monday 12 September 2005.

PubMed

Barrett, Alan D T; Monath, Thomas P; Barban, Veronique; Niedrig, Matthias; Teuwen, Dirk E

2007-04-12

Yellow fever (YF) is a major health problem in endemic regions of Africa and South America. It also poses a serious health risk to travellers to areas with endemic disease. Currently, there is no effective drug treatment for YF; however, 17D YF vaccines have demonstrated high rates of effectiveness and good safety profiles. This workshop was organized to review key data and issues about YF disease and currently available 17D YF vaccines. Starting with an overview of the current disease epidemiology in Africa and South America and a review of the safety data of 17D YF vaccines, data were then presented demonstrating the genetic stability of multiple production lots of a 17D YF vaccine, the immunological responses of healthy subjects post-vaccination and the long-term immunogenicity of 17D YF vaccines. Finally, the findings of the molecular characterization of 17D YF virus sub-strains recovered from rare, fatal cases of post-vaccination serious adverse events were presented. There was unanimous agreement that current 17D YF vaccines have a highly favourable benefit-risk profile when used in persons at risk of exposure to the YF virus, and that appropriate use of 17D YF vaccines will minimize the occurrence of serious adverse events post-vaccination.

Characterization and efficacy determination of commercially available Central American H5N2 avian influenza vaccines for poultry.

PubMed

Eggert, Dawn; Thomas, Colleen; Spackman, Erica; Pritchard, Nikki; Rojo, Francisco; Bublot, Michel; Swayne, David E

2010-06-23

A poultry vaccination program was implemented in Central America beginning in January 1995 to control both H5N2 low (LPAI) and high pathogenicity avian influenza. This study was conducted to identify seed strain composition and the efficacy of 10 commercially available H5 vaccines against challenge with H5N2 LPAI viruses isolated from Latin America in 2003. The original 1994 vaccine seed virus in commercial inactivated vaccines did not significantly reduce challenge virus shed titers. However, two seed strains of inactivated vaccines, genetically more closely related to the challenge virus, did significantly reduce titers of challenge virus shed from respiratory tract. In addition, a live recombinant fowlpox virus vaccine containing a more distantly related Eurasian lineage H5 gene insert significantly reduced respiratory shedding as compared to sham vaccinates. These results demonstrate the feasibility of identifying vaccine seed strains in commercial finished products for regulatory verification and the need for periodic challenge testing against current field strains in order to select efficacious vaccine seed strains. (c) 2010 Elsevier Ltd. All rights reserved.

Porcine Circovirus Type 2 (PCV2) Vaccines in the Context of Current Molecular Epidemiology.

PubMed

Karuppannan, Anbu K; Opriessnig, Tanja

2017-05-06

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen and, although small, it has the highest evolution rate among DNA viruses. Since the discovery of PCV2 in the late 1990s, this minimalistic virus with a 1.7 kb single-stranded DNA genome and two indispensable genes has become one of the most important porcine pathogens, and presently is subjected to the highest volume of prophylactic intervention in the form of vaccines in global swine production. PCV2 can currently be divided into five different genotypes, PCV2a through PCV2e. It is well documented that PCV2 continues to evolve, which is reflected by changes in the prevalence of genotypes. During 2006, commercial vaccines for PCV2 were introduced on a large scale in a pig population mainly infected with PCV2b. Since 2012, the PCV2d genotype has essentially replaced the previously predominant PCV2b genotype in North America and similar trends are also documented in other geographic regions such as China and South Korea. This is the second major PCV2 genotype shift since the discovery of the virus. The potential increase in virulence of the emergent PCV2 genotype and the efficacy of the current vaccines derived from PCV2a genotype against the PCV2d genotype viruses has received considerable attention. This review attempts to synthesize the understanding of PCV2 biology, experimental studies on the antigenic variability, and molecular epidemiological analysis of the evolution of PCV2 genotypes.

Porcine Circovirus Type 2 (PCV2) Vaccines in the Context of Current Molecular Epidemiology

PubMed Central

Karuppannan, Anbu K.; Opriessnig, Tanja

2017-01-01

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen and, although small, it has the highest evolution rate among DNA viruses. Since the discovery of PCV2 in the late 1990s, this minimalistic virus with a 1.7 kb single-stranded DNA genome and two indispensable genes has become one of the most important porcine pathogens, and presently is subjected to the highest volume of prophylactic intervention in the form of vaccines in global swine production. PCV2 can currently be divided into five different genotypes, PCV2a through PCV2e. It is well documented that PCV2 continues to evolve, which is reflected by changes in the prevalence of genotypes. During 2006, commercial vaccines for PCV2 were introduced on a large scale in a pig population mainly infected with PCV2b. Since 2012, the PCV2d genotype has essentially replaced the previously predominant PCV2b genotype in North America and similar trends are also documented in other geographic regions such as China and South Korea. This is the second major PCV2 genotype shift since the discovery of the virus. The potential increase in virulence of the emergent PCV2 genotype and the efficacy of the current vaccines derived from PCV2a genotype against the PCV2d genotype viruses has received considerable attention. This review attempts to synthesize the understanding of PCV2 biology, experimental studies on the antigenic variability, and molecular epidemiological analysis of the evolution of PCV2 genotypes. PMID:28481275

The Effects of Anti-Vaccine Conspiracy Theories on Vaccination Intentions

PubMed Central

Jolley, Daniel; Douglas, Karen M.

2014-01-01

The current studies investigated the potential impact of anti-vaccine conspiracy beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination intentions. In Study 1, British parents completed a questionnaire measuring beliefs in anti-vaccine conspiracy theories and the likelihood that they would have a fictitious child vaccinated. Results revealed a significant negative relationship between anti-vaccine conspiracy beliefs and vaccination intentions. This effect was mediated by the perceived dangers of vaccines, and feelings of powerlessness, disillusionment and mistrust in authorities. In Study 2, participants were exposed to information that either supported or refuted anti-vaccine conspiracy theories, or a control condition. Results revealed that participants who had been exposed to material supporting anti-vaccine conspiracy theories showed less intention to vaccinate than those in the anti-conspiracy condition or controls. This effect was mediated by the same variables as in Study 1. These findings point to the potentially detrimental consequences of anti-vaccine conspiracy theories, and highlight their potential role in shaping health-related behaviors. PMID:24586574

Vaccine chronicle in Japan.

PubMed

Nakayama, Tetsuo

2013-10-01

The concept of immunization was started in Japan in 1849 when Jenner's cowpox vaccine seed was introduced, and the current immunization law was stipulated in 1948. There have been two turning points for amendments to the immunization law: the compensation remedy for vaccine-associated adverse events in 1976, and the concept of private vaccination in 1994. In 1992, the regional Court of Tokyo, not the Supreme Court, decided the governmental responsibility on vaccine-associated adverse events, which caused the stagnation of vaccine development. In 2010, many universal vaccines became available as the recommended vaccines, but several vaccines, including mumps, zoster, hepatitis B, and rota vaccines, are still voluntary vaccines, not universal routine applications. In this report, immunization strategies and vaccine development are reviewed for each vaccine item and future vaccine concerns are discussed.

Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013--recommendations.

PubMed

2015-01-01

This article presents the World Health Organizations (WHO) evidence and recommendations for the use of yellow fever (YF) vaccination from "Vaccines and vaccination against yellow fever: WHO Position Paper - June 2013" published in the Weekly Epidemiological Record. This position paper summarizes the WHO position on the use of YF vaccination, in particular that a single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary. The current document replaces the position paper on the use of yellow fever vaccines and vaccination published in 2003. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014. Published by Elsevier Ltd.

Current Assessment of Yellow Fever and Yellow Fever Vaccine.

PubMed

Lefeuvre, Anabelle; Marianneau, Philippe; Deubel, Vincent

2004-04-01

Yellow fever (YF) is a mosquito-borne viral illness that causes hemorrhagic fever in tropical Africa and South America. Although a very safe and efficient vaccine (17D) is available, it is underused. An estimated 200,000 people are still infected annually, and YF remains a major public health concern. This article reviews the recent data on YF epidemiology, virology, and immunity, and analyzes the rare postvaccination adverse effects that have been recently reported. YF vaccine should be included in the expanded program of immunization for children and sustained for people living in or traveling to endemic areas. A surveillance of vaccinated people also should be reinforced. New research programs should be developed to identify molecular markers of YF virus tropism and attenuation, and to understand mechanisms of host responses to virus infection.

Nicotine vaccines: Will smokers take a shot at quitting?

PubMed Central

Lerman, Caryn; Cappella, Joseph N.

2010-01-01

Introduction: A vaccine against nicotine may soon be available to smokers who want to quit. The vaccine stimulates the production of antibodies that bind to nicotine, thereby impeding nicotine from crossing the blood-brain barrier and exerting psychoactive effects. The primary purpose of this study was to evaluate intentions to try a nicotine vaccine if one were to become available among a nationally representative sample of smokers. The secondary purpose was to assess whether information about genetic susceptibility to nicotine addiction had an effect on smokers’ interest in receiving the vaccine. Methods: Four hundred and twenty-seven adults were randomized to read one of two versions of a short description about the vaccine. One version framed addiction as genetically influenced, while the other framed it as environmentally influenced. Smokers were then asked about their intentions to use a nicotine vaccine if one were to become available in the future. Results: Across both groups, 53% indicated that they would be likely or very likely to try the vaccine. Using multivariate linear regression, the strongest predictors of vaccination intention were having a favorable attitude toward a nicotine vaccine (β = .41) and having a favorable attitude toward vaccination in general (β = .22). There were no significant effects of the framing conditions on intention to receive the vaccine. Discussion: Intentions to try a nicotine vaccine as a cessation method are relatively high among smokers. If the vaccine becomes available, specific groups of smokers may be more interested than others; education and recruitment efforts could be targeted appropriately. PMID:20185516

[Current status in the commercialization and application of genetically modified plants and their effects on human and livestock health and phytoremediation].

PubMed

Yoshimatsu, Kayo; Kawano, Noriaki; Kawahara, Nobuo; Akiyama, Hiroshi; Teshima, Reiko; Nishijima, Masahiro

2012-01-01

Developments in the use of genetically modified plants for human and livestock health and phytoremediation were surveyed using information retrieved from Entrez PubMed, Chemical Abstracts Service, Google, congress abstracts and proceedings of related scientific societies, scientific journals, etc. Information obtained was classified into 8 categories according to the research objective and the usage of the transgenic plants as 1: nutraceuticals (functional foods), 2: oral vaccines, 3: edible curatives, 4: vaccine antigens, 5: therapeutic antibodies, 6: curatives, 7: diagnostic agents and reagents, and 8: phytoremediation. In total, 405 cases were collected from 2006 to 2010. The numbers of cases were 120 for nutraceuticals, 65 for oral vaccines, 25 for edible curatives, 36 for vaccine antigens, 36 for therapeutic antibodies, 76 for curatives, 15 for diagnostic agents and reagents, and 40 for phytoremediation (sum of each cases was 413 because some reports were related to several categories). Nutraceuticals, oral vaccines and curatives were predominant. The most frequently used edible crop was rice (51 cases), and tomato (28 cases), lettuce (22 cases), potato (18 cases), corn (15 cases) followed.

Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

PubMed

Thacker, Eileen; Janke, Bruce

2008-02-15

Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

Immunogenetics of Seasonal Influenza Vaccine Response*

PubMed Central

Poland, Gregory A.; Ovsyannikova, Inna G.; Jacobson, Robert M.

2008-01-01

Seasonal influenza causes significant morbidity, mortality, and economic costs. Vaccines against influenza, though both safe and effective, are imperfect. Notably, these vaccines result in significant immune response variability across the population. The mechanism for this variability, in part, appears to lie in the polymorphisms of key immune response genes. Despite the importance of this variability, little in the way of genetic polymorphisms and its association with vaccine immune response to viral vaccines has been performed. Herein, we review and synthesize what is known about the immune response pathway and influenza viral immunity and then present original data from our laboratory on the immunogenetic relationships between HLA, cytokine and cytokine receptor gene polymorphisms and the variations in humoral immune response to inactivated seasonal influenza vaccine. Finally, we propose that a better understanding of vaccine immunogenetics offers insight towards the development of better influenza vaccines. PMID:19230157

Optimization model of vaccination strategy for dengue transmission

NASA Astrophysics Data System (ADS)

Widayani, H.; Kallista, M.; Nuraini, N.; Sari, M. Y.

2014-02-01

Dengue fever is emerging tropical and subtropical disease caused by dengue virus infection. The vaccination should be done as a prevention of epidemic in population. The host-vector model are modified with consider a vaccination factor to prevent the occurrence of epidemic dengue in a population. An optimal vaccination strategy using non-linear objective function was proposed. The genetic algorithm programming techniques are combined with fourth-order Runge-Kutta method to construct the optimal vaccination. In this paper, the appropriate vaccination strategy by using the optimal minimum cost function which can reduce the number of epidemic was analyzed. The numerical simulation for some specific cases of vaccination strategy is shown.

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

PubMed

Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

2016-09-01

Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

The current state of therapeutic and T cell-based vaccines against human papillomaviruses

PubMed Central

Yang, Andrew; Farmer, Emily; Lin, John; Wu, T-C.; Hung, Chien-Fu

2016-01-01

Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. PMID:27932207

The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

PubMed

Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

2016-09-09

Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

Vaccinia Virus Vaccines: Past, Present and Future

PubMed Central

Jacobs, Bertram L.; Langland, Jeffrey O.; Kibler, Karen V.; Denzler, Karen L.; White, Stacy D.; Holechek, Susan A.; Wong, Shukmei; Huynh, Trung; Baskin, Carole R.

2009-01-01

Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third- and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence. PMID:19563829

Genomic Variation between Genetic lines of White Leghorns Differed in Resistance to Marek’s Disease

USDA-ARS?s Scientific Manuscript database

Genetic resistance to avian tumor virus-induced tumorigenesis and vaccine protective efficacy preventing such tumorigenicity are determined by multiple factors including host genetics, viral virulence, dose of challenge viruses, type of vaccine, vaccine dosage, and interval between vaccination and v...

Isolation and genetic characterization of a novel 2.2.1.2a H5N1 virus from a vaccinated meat-turkeys flock in Egypt.

PubMed

Salaheldin, Ahmed H; Veits, Jutta; Abd El-Hamid, Hatem S; Harder, Timm C; Devrishov, Davud; Mettenleiter, Thomas C; Hafez, Hafez M; Abdelwhab, Elsayed M

2017-03-09

Vaccination of poultry to control highly pathogenic avian influenza virus (HPAIV) H5N1 is used in several countries. HPAIV H5N1 of clade 2.2.1 which is endemic in Egypt has diversified into two genetic clades. Clade 2.2.1.1 represents antigenic drift variants in vaccinated commercial poultry while clade 2.2.1.2 variants are detected in humans and backyard poultry. Little is known about H5N1 infection in vaccinated turkeys under field conditions. Here, we describe an HPAI H5N1 outbreak in a vaccinated meat-turkey flock in Egypt. Birds were vaccinated with inactivated H5N2 and H5N1 vaccines at 8 and 34 days of age, respectively. At 72 nd day of age (38 days post last vaccination), turkeys exhibited mild respiratory signs, cyanosis of snood and severe congestion of the internal organs. Survivors had a reduction in feed consumption and body gain. A mortality of ~29% cumulated within 10 days after the onset of clinical signs. Laboratory diagnosis using RT-qPCRs revealed presence of H5N1 but was negative for H7 and H9 subtypes. A substantial antigenic drift against different serum samples from clade 2.2.1.1 and clade 2.3.4.4 was observed. Based on full genome sequence analysis the virus belonged to clade 2.2.1.2 but clustered with recent H5N1 viruses from 2015 in poultry in Israel, Gaza and Egypt in a novel subclade designated here 2.2.1.2a which is distinct from 2014/2015 2.2.1.2 viruses. These viruses possess 2.2.1.2 clade-specific genetic signatures and also mutations in the HA similar to those in clade 2.2.1.1 that enabled evasion from humoral immune response. Taken together, this manuscript describes a recent HPAI H5N1 outbreak in vaccinated meat-turkeys in Egypt after infection with a virus representing novel distinct 2.2.1.2a subclade. Infection with HPAIV H5N1 in commercial turkeys resulted in significant morbidity and mortality despite of vaccination using H5 vaccines. The isolated virus showed antigenic drift and clustered in a novel cluster designated here

Universal influenza vaccines: Shifting to better vaccines.

PubMed

Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

2016-06-03

Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

A decade of vaccines: Integrating immunology and vaccinology for rational vaccine design.

PubMed

D'Argenio, David A; Wilson, Christopher B

2010-10-29

Vaccination stands as one of the most successful public health measures of the last century. New approaches will be needed, however, to develop highly effective vaccines to prevent tuberculosis, HIV-AIDS, and malaria and to eradicate polio. Current advances in immunology and technology have set the stage for rational vaccine design to begin a "Decade of Vaccines." Copyright © 2010 Elsevier Inc. All rights reserved.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

PubMed

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

PubMed Central

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. PMID:29403503

Virus like particles as a platform for cancer vaccine development.

PubMed

Ong, Hui Kian; Tan, Wen Siang; Ho, Kok Lian

2017-01-01

Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative. In addition, they can be engineered to display multiple, highly ordered heterologous epitopes or peptides in order to optimize the antigenicity and immunogenicity of the displayed entities. Like native viruses, specific epitopes displayed on VLPs can be taken up, processed, and presented by antigen-presenting cells to elicit potent specific humoral and cell-mediated immune responses. Several studies also indicated that VLPs could overcome the immunosuppressive state of the tumor microenvironment and break self-tolerance to elicit strong cytotoxic lymphocyte activity, which is crucial for both virus clearance and destruction of cancerous cells. Collectively, these unique characteristics of VLPs make them optimal cancer vaccine candidates. This review discusses current progress in the development of VLP-based cancer vaccines and some potential drawbacks of VLPs in cancer vaccine development. Extracellular vesicles with close resembling to viral particles are also discussed and compared with VLPs as a platform in cancer vaccine developments.

Bacterial Artificial Chromosome Clones of Viruses Comprising the Towne Cytomegalovirus Vaccine

PubMed Central

Cui, Xiaohong; Adler, Stuart P.; Davison, Andrew J.; Smith, Larry; Habib, EL-Sayed E.; McVoy, Michael A.

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines. PMID:22187535

Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine.

PubMed

Cui, Xiaohong; Adler, Stuart P; Davison, Andrew J; Smith, Larry; Habib, El-Sayed E; McVoy, Michael A

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Influenza Vaccines: Challenges and Solutions

PubMed Central

Houser, Katherine; Subbarao, Kanta

2015-01-01

Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases

PubMed Central

Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

PubMed

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

PubMed

Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

2017-08-01

An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.

PubMed

Gershwin, Laurel J

2018-03-01

Vaccines are important for providing protection from infectious diseases. Vaccination initiates a process that stimulates development of a robust and long-lived immune response to the disease agents in the vaccine. Side effects are sometimes associated with vaccination. These vary from development of acute hypersensitivity responses to vaccine components to local tissue reactions that are annoying but not significantly detrimental to the patient. The pathogenesis of these responses and the consequent clinical outcomes are discussed. Overstimulation of the immune response and the potential relationship to autoimmunity is evaluated in relation to genetic predisposition. Copyright © 2017 Elsevier Inc. All rights reserved.

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

Marker vaccine strategies and candidate CSFV marker vaccines.

PubMed

Dong, Xiao-Nan; Chen, Ying-Hua

2007-01-04

Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new

Thiomersal-containing vaccines - a review of the current state of knowledge.

PubMed

Gołoś, Aleksandra; Lutyńska, Anna

2015-01-01

Thiomersal is an organomercury compound known for its antiseptic and antifungal properties and used as an antibacterial agent in pharmaceutical products, including vaccines and other injectable biological products. In recent years, concerns about the possible link between immunization with thiomersal-containing vaccines and autism development have grown. Many case-control and cohort studies have been conducted on a number of populations, and none of them have confirmed the hypothetical relation between thiomersal and increased risk of autism spectrum disorders (ASDs) development. It is also confirmed by the fact, that since 1999, number of thiomersal-containing vaccines used worldwide is decreasing year by year, while the prevalence of ASDs cases is rising. There are no contraindications to the use of vaccines with thiomersal in infants, children and non-pregnant women. The risk of serious complications associated with the development of diseases in unvaccinated individuals far outweighs the potential risk of adverse consequences associated with immunization with thiomersal-containing vaccines.

Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

PubMed

Issa, Mohammad Nouh; Ashhab, Yaqoub

2016-09-22

Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic variability of porcine circovirus 2 (PCV2) field isolates from vaccinated and non-vaccinated pig herds in Germany.

PubMed

Reiner, Gerald; Hofmeister, Regina; Willems, Hermann

2015-10-22

Porcine circovirus 2 (PCV2) is responsible for a wide range of associated diseases (PCVD) affecting swine production worldwide. Highly efficient commercial vaccines induce protective immunity, but PCV2 is still circulating in vaccinated farms. Thus, and because of the viruś high mutation rate, recent findings provide concerns about PCV2 strains capable to escape vaccination. Based on 2156 samples from individual pigs of 315 herds from Germany we describe a high effectivity of vaccination between 2008 and the third quarter of 2011. In this period, virus load dropped continuously and at the end of this period it hardly reached the limit of quantification. Thereafter, virus loads re-increased, although most of the herds were still vaccinated. Sixty-two randomly selected samples from vaccinated (n=28) and non-vaccinated (n=26) herds between 2008 and 2012 were completely sequenced. As compared to the PCV2b reference sequence 259 polymorphisms were detected. Polymorhisms were analysed for associations to vaccination status, genotype (PCV2a/PCV2b), and virus load. PCV2a sequences were significantly repelled by PCV2b. One SNP at position 1182 (g.1182G>T), involved in capsid epitope formation, was significantly associated with the PCV2 genotype (2a/2b). Moreover, this SNP was affected by vaccination, with effects on allele frequencies and viral load, independent from the PCV2 genotype (2a/2b). We conclude that there is indeed evidence for a selectional impact of vaccination on the PCV2 sequence, especially on nucleotides involved in epitope formation. Such variation might be responsible for the observed re-increase of PCV2-loads in samples from the end of 2011 in Germany. Copyright © 2015 Elsevier B.V. All rights reserved.

The current state of therapeutic and T cell-based vaccines against human papillomaviruses.

PubMed

Yang, Andrew; Farmer, Emily; Lin, John; Wu, T-C; Hung, Chien-Fu

2017-03-02

Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

DNA vaccines in veterinary use

PubMed Central

Redding, Laurel; Werner, David B

2015-01-01

DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

[Severe Yellow fever vaccine-associated disease: a case report and current overview].

PubMed

Slesak, Günther; Gabriel, Martin; Domingo, Cristina; Schäfer, Johannes

2017-08-01

History and physical examination  A 56-year-old man developed high fever with severe headaches, fatigue, impaired concentration skills, and an exanthema 5 days after a yellow fever (YF) vaccination. Laboratory tests  Liver enzymes and YF antibody titers were remarkably elevated. YF vaccine virus was detected in urine by PCR. Diagnosis and therapy  Initially, severe YF vaccine-associated visceral disease was suspected and treated symptomatically. Clinical Course  His fever ceased after 10 days in total, no organ failure developed. However, postencephalitic symptoms persisted with fatigue and impaired concentration, memory, and reading skills and partly incapability to work for over 3 months. A diagnosis was made of suspected YF vaccine-associated neurotropic disease. Conclusion  Severe vaccine-derived adverse effects need to be considered in the indication process for YF vaccination. © Georg Thieme Verlag KG Stuttgart · New York.

[Vaccines and autism: a myth to debunk?].

PubMed

Battistella, Melania; Carlino, Cristiana; Dugo, Valentina; Ponzo, Patrizia; Franco, Elisabetta

2013-01-01

Thanks to vaccinations the incidence of many seriously debilitating or life threatening diseases and the resulting infant mortality or disability have been drastically reduced. In populations, who are no more aware of the risk of these infections, the attitude of suspicion and fear towards the vaccinations is expanding and in some cases reaches a worldwide media coverage as was the case for the measles, mumps and rubella vaccine (MMR). In 1998, a British doctor, Andrew Wakefield, and co-authors, published in "Lancet" a study in which he suggested the existence of "a new variant of autism" associated with intestinal inflammation. He proposed the administration of the MMR vaccine as a possible. cause of the inflammatory process. The hypothesis suggested by Wakefield led to a drastic drop in vaccination coverage in the UK and to the failure to achieve adequate levels of immunization in many countries, with a consequent increase in the incidence of measles and its complications. Wakefield work stimulated a broad discussion in the scientific community and many studies conducted over the next few years contradicted the research results of the English physician. In 2004, journalist Brian Deer conducted an accurate investigation that revealed how the Wakefield research presented many not regular aspects and was performed with predominantly economic objectives. In 2010, Wakefield was expelled from the General Medical Council, while the "Lancet" retracted the paper. The scientific research conducted in recent years confirm the inconsistency of the relationship between MMR vaccine and autism. The possible association with other factors, such as autoimmune processes, hyperactivation of mast cells in the hypothalamus, use of paracetamol in genetically predisposed children are currently investigated.

Personalized vaccines: the emerging field of vaccinomics

PubMed Central

Poland, Gregory A; Ovsyannikova, Inna G; Jacobson, Robert M

2010-01-01

The next ‘golden age’ in vaccinology will be ushered in by the new science of vaccinomics. In turn, this will inform and allow the development of personalized vaccines, based on our increasing understanding of immune response phenotype: genotype information. Rapid advances in developing such data are already occurring for hepatitis B, influenza, measles, mumps, rubella, anthrax and smallpox vaccines. In addition, newly available data suggest that some vaccine-related adverse events may also be genetically determined and, therefore, predictable. This paper reviews the basis and logic of personalized vaccines, and describes recent advances in the field. PMID:18847302

Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

PubMed

Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle

2015-10-06

RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination.

PubMed

Lee, Donghoon; Park, Sang Min

2016-01-01

To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country's current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer's perspectives and evaluated by Disability Adjusted Life Year (DALY). The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer's perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer's perspective. Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.

Strategies for new and improved vaccines against ticks and tick-borne diseases.

PubMed

de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C

2016-12-01

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.

Bringing DNA vaccines closer to commercial use.

PubMed

Carvalho, Joana A; Prazeres, Duarte M F; Monteiro, Gabriel A

2009-10-01

Progress in the application of DNA vaccines as an immunization protocol is evident from the increasing number of such vaccines under evaluation in clinical trials and by the recent approval of several DNA vaccine products for veterinary applications. DNA vaccine technology offers important therapeutic and commercial advantages compared with conventional approaches, including the opportunity to target pathogens characterized by significant genetic diversity using a safe immunization platform, and the ability to use a simple, rapid and well-characterized production method. However, further optimization of DNA vaccine technology through the use of improved constructs, delivery systems and immunization protocols is necessary to clinically achieve the promising results that have been demonstrated in preclinical models.

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

PubMed

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

Chinese vaccine products go global: vaccine development and quality control.

PubMed

Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

2015-05-01

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

Plastid Molecular Pharming I. Production of Oral Vaccines via Plastid Transformation.

PubMed

Berecz, Bernadett; Zelenyánszki, Helga; Pólya, Sára; Tamás-Nyitrai, Cecília; Oszvald, Mária

2017-01-01

Vaccines produced in plants have opened up new opportunities in vaccination. Among the various categories of vaccines, the recombinant vaccine is generally regarded as the most economical and safest type because it cannot cause disease and does not require large-scale cultivation of pathogens. Due to the low cost of their cultivation, plants may represent viable alternative platforms for producing subunit vaccines. Genetic engineering of plastids is the innovation of the last three decades and has numerous benefits when compared to nuclear transformation. Due to the high level of expression, oral vaccines produced in transplastomic plants do not have to be purified as they can be consumed raw, which, therefore, reduces the cost of preparation, transportation and handling of the vaccines. Oral vaccination also excludes the risk of other infections or contaminations, while compartmentation of the plant cell provides an excellent encapsulation to the antigen within the plastid. Herein we review the main biotechnological and immunological aspects of the progress achieved in the field of plastid derived edible vaccines during the last decade. As there is a public debate against genetically modified crops, the advantages and limitations of oral vaccines are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The dichotomy of pathogens and allergens in vaccination approaches

PubMed Central

Baird, Fiona J.; Lopata, Andreas L.

2014-01-01

Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of GardasilTM against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilized in the near future. PMID:25076945

Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

PubMed Central

Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo

2012-01-01

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.   Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531

Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.

PubMed

Maki, Joanne; Guiot, Anne-Laure; Aubert, Michel; Brochier, Bernard; Cliquet, Florence; Hanlon, Cathleen A; King, Roni; Oertli, Ernest H; Rupprecht, Charles E; Schumacher, Caroline; Slate, Dennis; Yakobson, Boris; Wohlers, Anne; Lankau, Emily W

2017-09-22

RABORAL V-RG ® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control

Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

PubMed

Thiele, Sonja; Borschewski, Aljona; Küchler, Judit; Bieberbach, Marc; Voigt, Sebastian; Ehlers, Bernhard

2011-07-01

To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.

Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

PubMed

Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Sutter, Roland W; Wassilak, Steven G; Burns, Cara C

2016-08-05

In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4).

Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow.

PubMed

Vitaliti, Giovanna; Praticò, Andrea Domenico; Cimino, Carla; Di Dio, Giovanna; Lionetti, Elena; La Rosa, Mario; Leonardi, Salvatore

2013-02-14

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

Reemergence of recombinant vaccine-derived poliovirus outbreak in Madagascar.

PubMed

Rakoto-Andrianarivelo, Mala; Gumede, Nicksy; Jegouic, Sophie; Balanant, Jean; Andriamamonjy, Seta N; Rabemanantsoa, Sendraharimanana; Birmingham, Maureen; Randriamanalina, Bakolalao; Nkolomoni, Léon; Venter, Marietjie; Schoub, Barry D; Delpeyroux, Francis; Reynes, Jean-Marc

2008-05-15

After the 2001-2002 poliomyelitis outbreak due to recombinant vaccine-derived polioviruses (VDPVs) in the Toliara province of Madagascar, another outbreak reoccurred in the same province in 2005. We conducted epidemiological and virological investigations for each polio case patient and for their contacts. From May to August 2005, a total of 5 cases of acute flaccid paralysis were reported among unvaccinated or partially vaccinated children 2-3 years old. Type-3 or type-2 VDPV was isolated from case patients and from healthy contacts. These strains were classified into 4 recombinant lineages that showed complex mosaic genomic structures originating from different vaccine strain serotypes and probably from human enterovirus C (HEV-C) species. Genetic relatedness could be observed among these 4 lineages. Vaccination coverage of the population was very low (<50%). The broad distribution of VDPVs in the province and their close genetic relationship indicate intense and rapid cocirculation and coevolution of the vaccine strains and of their related HEV-C strains. The occurrence of an outbreak due to VDPV 3 years after a previous outbreak indicates that a short period with low vaccination coverage is enough to create favorable conditions for the emergence of VDPV in this setting.

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

PubMed

Lokugamage, Nandadeva; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

The current state of genetic counseling and newborn screening: an interview with Megan Tucker

PubMed Central

Tucker, Megan

2017-01-01

Megan Tucker talks to Francesca Lake, Managing Editor: A certified genetic counselor for over 10 years, Megan is currently the director of the Indiana State University Genetic Counseling Graduate Program and the Genetic Counseling Clinic at Union Hospital (Terre Haute, IN, USA). She began her career split between the Center for Prenatal Diagnosis and the Medical Genetics and Neurodevelopmental Center at St Vincent Hospital (Indianapolis, IN, USA). During this time she was instrumental in both the development of the statewide Perinatal Loss Evaluation Program and a hospital protocol to ensure collection of cord blood to allow time to effectively genetically evaluate babies. Her current clinical focus is in cancer and psychiatric genetic counseling. PMID:28883988

Repeated Vaccination Does Not Appear to Impact Upon Influenza Vaccine Effectiveness Against Hospitalization With Confirmed Influenza.

PubMed

Cheng, Allen C; Macartney, Kristine K; Waterer, Grant W; Kotsimbos, Tom; Kelly, Paul M; Blyth, Christopher C

2017-06-01

Annual influenza vaccine is recommended for those at greatest risk of severe influenza infection. Recent reports of a negative impact of serial influenza vaccination on vaccine effectiveness (VE) raises concerns about the recommendation for annual influenza vaccines, particularly in persons at greatest risk. The Influenza Complications Alert Network (FluCAN) is an Australian hospital-based sentinel surveillance program. In this observational study, cases were defined as subjects aged >9 years admitted with influenza confirmed by polymerase chain reaction. Controls were subjects with acute respiratory illness testing negative for influenza. Propensity scores were used to adjust for the likelihood of being vaccinated. VE was calculated as 1 - adjusted odds ratio of vaccination in cases compared with test-negative controls. Over 2010-2015, 6223 cases and 6505 controls were hospitalized with confirmed influenza and influenza test-negative acute respiratory illness, respectively. Following stratification by quintile of propensity score, site, and year, VE was estimated to be 43% (95% confidence interval [CI], 37%-49%) overall. VE was estimated to be 51% (95% CI, 45%-57%) in those vaccinated in both the current and previous season, compared with 33% (95% CI, 17%-47%) vaccinated in the current season only and 35% (95% CI, 21%-46%) in the previous season only. Similar results were observed for influenza A/H1N1, influenza A/H3N2, and influenza B strains. Vaccination in both the current and previous seasons was associated with a higher VE against hospitalization with influenza than vaccination in either single season. These findings reinforce current recommendations for annual influenza vaccination, particularly those at greatest risk of influenza disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Update on autism spectrum disorder: vaccines, genomes, and social skills training.

PubMed

McGuinness, Teena M

2015-04-01

Despite making significant progress in understanding autism spectrum disorder (ASD) and its genetic underpinnings, controversy remains regarding ASD and its historical, erroneous association with vaccines. This controversy includes the latest anti-vaccine movement that caused a recurrence of the almost vanquished measles and mumps diseases. The history of ASD, complexities of research involving ASD genetics, and benefits of social skills training are explored. Copyright 2015, SLACK Incorporated.

Vaccines against human diarrheal pathogens

PubMed Central

Böhles, Nathalie; Böhles, Nathalie; Busch, Kim; Busch, Kim; Hensel, Michael; Hensel, Michael

2014-01-01

Worldwide, nearly 1.7 billion people per year contract diarrheal infectious diseases (DID) and almost 760 000 of infections are fatal. DID are a major problem in developing countries where poor sanitation prevails and food and water may become contaminated by fecal shedding. Diarrhea is caused by pathogens such as bacteria, protozoans and viruses. Important diarrheal pathogens are Vibrio cholerae, Shigella spp. and rotavirus, which can be prevented with vaccines for several years. The focus of this review is on currently available vaccines against these three pathogens, and on development of new vaccines. Currently, various types of vaccines based on traditional (killed, live attenuated, toxoid or conjugate vaccines) and reverse vaccinology (DNA/mRNA, vector, recombinant subunit, plant vaccines) are in development or already available. Development of new vaccines demands high levels of knowledge, experience, budget, and time, yet promising new vaccines often fail in preclinical and clinical studies. Efficacy of vaccination also depends on the route of delivery, and mucosal immunization in particular is of special interest for preventing DID. Furthermore, adjuvants, delivery systems and other vaccine components are essential for an adequate immune response. These aspects will be discussed in relation to the improvement of existing and development of new vaccines against DID. PMID:24861668

The impact of making vaccines thermostable in Niger's vaccine supply chain.

PubMed

Lee, Bruce Y; Cakouros, Brigid E; Assi, Tina-Marie; Connor, Diana L; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R; Pierre, Lionel; Brown, Shawn T

2012-08-17

Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%. Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. Copyright © 2012 Elsevier Ltd. All rights reserved.